Anesthesia & Analgesia

Gene Variants in Hepatic Metabolism, Gamma-Aminobutyric Acid-ergic Reward, and Prostaglandin Pathways in Opioid-Consuming and Opioid-Naïve Patients Presenting for Lower Extremity Total Joint Replacement Gene variants may contribute to individual differences in the experience of pain and the efficacy and reward of treatments. We explored gene variation in opioid-naïve and opioid-consuming patients undergoing elective lower extremity total joint replacement. We focused on 3 gene pathways including prostaglandin, gamma-aminobutyric acid (GABA)-ergic reward, and hepatic metabolism pathways. We report that for genes with possible or probable deleterious impact in these 3 pathways, opioid consumers had more gene variants than opioid-naïve patients (median 3 vs 1, P = .0092). We conclude that chronic opiate users may have genetic susceptibility to altered responses in reward/dependency and pain/inflammation pathways. Accepted for publication May 14, 2019. Funding: Departmental/institutional. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.anesthesia-analgesia.org). Clinical trial number and registry URL: This study is not subject to clinicaltrials.gov review as the study is not a clinical trial and does not involve an intervention or investigational use of a device or drug. Reprints will not be available from the authors. Address correspondence to Ami R. Stuart, PhD, Department of Anesthesiology, University of Utah, 30 N 1900 E RM 3C444, Salt Lake City, UT 84112. Address e-mail to ami.stuart@hsc.utah.edu. © 2019 International Anesthesia Research Society

Adultification of Black Children in Pediatric Anesthesia BACKGROUND: Unconscious racial bias in anesthesia care has been shown to exist. We hypothesized that black children may undergo inhalation induction less often, receive less support from child life, have fewer opportunities to have a family member present for induction, and receive premedication with oral midazolam less often. METHODS: We retrospectively collected data on those <18 years of age from January 1, 2012 to January 1, 2018 including age, sex, race, height, weight, American Society of Anesthesiologists (ASA) physical status, surgical service, and deidentified anesthesiology attending physician. Outcome data included mask versus intravenous induction, midazolam premedication, child life consultation, and family member presence. Racial differences between all outcomes were assessed in the cohort using a multivariable logistic regression model. RESULTS: A total of 33,717 Caucasian and 3901 black children were eligible for the study. For the primary outcome, black children 10–14 years were 1.3 times more likely than Caucasian children to receive mask induction (adjusted odds ratio [AOR], 1.3; 95% confidence interval [CI], 1.1–1.6; P = .001). Child life consultation was poorly documented (<0.5%) and not analyzed. Black children <15 years of age were at least 31% less likely than Caucasians to have a family member present for induction (AOR range, 0.4–0.6; 95% CI range, 0.31–0.84; P < .010). Black children <5 years of age were 13% less likely than Caucasians to have midazolam given preoperatively (AOR, 0.9; 95% CI, 0.8–0.9; P = .012). CONCLUSIONS: This study suggests that disparities in strategies for mitigating anxiety in the peri-induction period exist and adultification may be 1 cause for this bias. Black children 10 to 14 years of age are 1.3 times as likely as their Caucasian peers to be offered inhalation induction to reduce anxiety. However, black children are less likely to receive premedication with midazolam in the perioperative period or to have family members present at induction. The cause of this difference is unclear, and further prospective studies are needed to fully understand this difference. Accepted for publication May 7, 2019. Funding: None. The authors declare no conflicts of interest. This report describes human research. Institutional review board (IRB) contact information: Institutional Review Boards of the UM Medical School, 2800 Plymouth Rd, Building 200, Room 2086, Ann Arbor, MI 48109; e-mail: irbmed@umich.edu. The requirement for written informed consent was waived by the IRB. This report describes an observational clinical study. The author states that the report includes every item in the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) checklist for case–control observational clinical studies. Reprints will not be available from the authors. Address correspondence to Anne Baetzel, MD, Department of Anesthesiology, University of Michigan Medical School, 4–911 CS Mott Children's Hospital, 1540 E Medical Center Dr, Ann Arbor, MI 48109. Address e-mail to abaetzel@med.umich.edu. © 2019 International Anesthesia Research Society

Anesthesia Provider Training and Practice Models: A Survey of Africa BACKGROUND: In Africa, most countries have fewer than 1 physician anesthesiologist (PA) per 100,000 population. Nonphysician anesthesia providers (NPAPs) play a large role in the workforce of many low- and middle-income countries (LMICs), but little information has been systematically collected to describe existing human resources for anesthesia care models. An understanding of existing PA and NPAP training pathways and roles is needed to inform anesthesia workforce planning, especially for critically underresourced countries. METHODS: Between 2016 and 2018, we conducted electronic, phone, and in-person surveys of anesthesia providers in Africa. The surveys focused on the presence of anesthesia training programs, training program characteristics, and clinical scope of practice after graduation. RESULTS: One hundred thirty-one respondents completed surveys representing data for 51 of 55 countries in Africa. Most countries had both PA and NPAP training programs (57%; mean, 1.6 pathways per country). Thirty distinct training pathways to become an anesthesia provider could be discriminated on the basis of entry qualification, duration, and qualification gained. Of these 30 distinct pathways, 22 (73%) were for NPAPs. Physician and NPAP program durations were a median of 48 and 24 months (ranges: 36–72, 9–48), respectively. Sixty percent of NPAP pathways required a nursing background for entry, and 60% conferred a technical (eg, diploma/license) qualification after training. Physicians and NPAPs were trained to perform most anesthesia tasks independently, though few had subspecialty training (such as regional or cardiac anesthesia). CONCLUSIONS: Despite profound anesthesia provider shortages throughout Africa, most countries have both NPAP and PA training programs. NPAP training pathways, in particular, show significant heterogeneity despite relatively similar scopes of clinical practice for NPAPs after graduation. Such heterogeneity may reflect the varied needs and resources for different settings, though may also suggest lack of consensus on how to train the anesthesia workforce. Lack of consistent terminology to describe the anesthesia workforce is a significant challenge that must be addressed to accelerate workforce research and planning efforts. Accepted for publication May 16, 2019. Funding: This work received funding Hellman Family Foundation and received additional funds from the International Relations Committee of the Association of Anaesthetists/Royal College of Anesthetists for travel support. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.anesthesia-analgesia.org). T. J. Law and F. Bulamba contributed equally and share first authorship. Reprints will not be available from the authors. Address correspondence to Tyler J. Law, MD, Division of Global Health Equity, Department of Anesthesia and Perioperative Care, University of California San Francisco, 1001 Potrero Ave, Bldg 5, Rm 3C38, San Francisco, CA 94110. Address e-mail to tyler.law@ucsf.edu. © 2019 International Anesthesia Research Society

Comparison of 3 Methods to Assess Occupational Sevoflurane Exposure in Abdominal Surgeons: A Single-Center Observational Pilot Study BACKGROUND: Studies demonstrated that operating room personnel are exposed to anesthetic gases such as sevoflurane (SEVO). Measuring the gas burden is essential to assess the exposure objectively. Air pollution measurements and the biological monitoring of urinary SEVO and its metabolite hexafluoroisopropanol (HFIP) are possible approaches. Calculating the mass of inhaled SEVO is an alternative, but its predictive power has not been evaluated. We investigated the SEVO burdens of abdominal surgeons and hypothesized that inhaled mass calculations would be better suited than pollution measurements in their breathing zones (25 cm around nose and mouth) to estimate urinary SEVO and HFIP concentrations. The effects of potentially influencing factors were considered. METHODS: SEVO pollution was continuously measured by photoacoustic gas monitoring. Urinary SEVO and HFIP samples, which were collected before and after surgery, were analyzed by a blinded environmental toxicologist using the headspace gas chromatography-mass spectrometry method. The mass of inhaled SEVO was calculated according to the formula mVA = cVA·V·t·ρ VA aer. (mVA: inhaled mass; cVA: volume concentration; V: respiratory minute volume; t: exposure time; and ρ VA aer.: gaseous density of SEVO). A linear multilevel mixed model was used for data analysis and comparisons of the different approaches. RESULTS: Eight surgeons performed 22 pancreatic resections. Mean (standard deviation [SD]) SEVO pollution was 0.32 ppm (0.09 ppm). Urinary SEVO concentrations were below the detection limit in all samples, whereas HFIP was detectable in 82% of the preoperative samples in a mean (SD) concentration of 8.53 µg·L−1 (15.53 µg·L−1; median: 2.11 µg·L−1, interquartile range [IQR]: 4.58 µg·L−1) and in all postoperative samples (25.42 µg·L−1 [21.39 µg·L−1]). The mean (SD) inhaled SEVO mass was 5.67 mg (2.55 mg). The postoperative HFIP concentrations correlated linearly to the SEVO concentrations in the surgeons' breathing zones (β = 216.89; P < .001) and to the calculated masses of inhaled SEVO (β = 4.17; P = .018). The surgeon's body mass index (BMI), age, and the frequency of surgeries within the last 24 hours before study entry did not influence the relation between HFIP concentration and air pollution or inhaled mass, respectively. CONCLUSIONS: The biological SEVO burden, expressed as urinary HFIP concentration, can be estimated by monitoring SEVO pollution in the personnel's individual breathing zone. Urinary SEVO was not an appropriate biomarker in this setting. Accepted for publication May 16, 2019. Funding: Departmental. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Jennifer Herzog-Niescery, MD, Department of Anesthesiology, Ruhr-University Bochum, St Josef-Hospital Bochum, Gudrunstraße 56, D-44791 Bochum, Germany. Address e-mail to j.herzog-niescery@klinikum-bochum.de © 2019 International Anesthesia Research Society

Impact of Anesthetics, Analgesics, and Perioperative Blood Transfusion in Pediatric Cancer Patients: A Comprehensive Review of the Literature Cancer is the leading cause of death by disease in developed countries. Children and adolescents with cancer need surgical interventions (ie, biopsy or major surgery) to diagnose, treat, or palliate their malignancies. Surgery is a period of high vulnerability because it stimulates the release of inflammatory mediators, catecholamines, and angiogenesis activators, which coincides with a period of immunosuppression. Thus, during and after surgery, dormant tumors or micrometastasis (ie, minimal residual disease) can grow and become clinically relevant metastasis. Anesthetics (ie, volatile agents, dexmedetomidine, and ketamine) and analgesics (ie, opioids) may also contribute to the growth of minimal residual disease or disease progression. For instance, volatile anesthetics have been implicated in immunosuppression and direct stimulation of cancer cell survival and proliferation. Contrarily, propofol has shown in vitro anticancer effects. In addition, perioperative blood transfusions are not uncommon in children undergoing cancer surgery. In adults, an association between perioperative blood transfusions and cancer progression has been described for some malignancies. Transfusion-related immunomodulation is one of the mechanisms by which blood transfusions can promote cancer progression. Other mechanisms include inflammation and the infusion of growth factors. In the present review, we discuss different aspects of tumorigenesis, metastasis, angiogenesis, the immune system, and the current studies about the impact of anesthetics, analgesics, and perioperative blood transfusions on pediatric cancer progression. Accepted for publication May 23, 2019. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Juan P. Cata, MD, Department of Anesthesiology and Perioperative Medicine, University of Texas MD Anderson Cancer Centre, 1515 Holcombe Blvd, Unit 409, Houston, TX 77005. Address e-mail to jcata@mdanderson.org. © 2019 International Anesthesia Research Society

In Response No abstract available

Sugammadex Administration in Pregnant Women and in Women of Reproductive Potential: A Narrative Review Since its clinical introduction in 2008, sugammadex has demonstrated a high degree of safety and superior effectiveness compared to neostigmine when used to antagonize muscle relaxation produced by steroid nondepolarizing neuromuscular blockers. This includes its use in special populations, such as the elderly, children over 2 years old, and patients with renal, hepatic, or lung disease. In contrast, clinical evidence guiding its use during pregnancy, in women of childbearing potential, and in lactating women, is sparse. An exception is administration at the end of surgery in parturients undergoing cesarean delivery (CD) with general anesthesia (GA), for whom effectiveness and safety evidence is rapidly accumulating. We review evidence regarding sugammadex rescue reversal shortly after high-dose rocuronium in cases of cannot intubate/cannot ventilate (CICV), the extent of placental transfer of maternally administered sugammadex, adverse fetal effects of sugammadex exposure, potential effects on maintenance of early pregnancy, and the extent of transfer to breast milk. Finally, many anesthesiologists appear to heed the manufacturer's warning regarding informing women of childbearing potential regarding the risk of hormone contraceptive failure after sugammadex exposure. We provide a medical ethics analysis of the ex post facto counseling commonly reported after sugammadex administration, which favors either preoperative discussion and shared decision making, or the decision by the physician to use neostigmine. This review highlights the disparity in evidence regarding sugammadex use in various contexts of female reproductive health, including current research gaps that prevent this population from sharing in the benefits of sugammadex enjoyed by most perioperative patients. Accepted for publication May 20, 2019. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Michael G. Richardson, MD, Division of Obstetric Anesthesiology, Vanderbilt University Medical Center, 4202 VUH, Nashville, TN 37232. Address e-mail to m.richardson@vumc.org. © 2019 International Anesthesia Research Society

BOSTN Bundle Intervention for Perioperative Screening and Management of Patients With Suspected Obstructive Sleep Apnea: A Hospital Registry Study BACKGROUND: We developed and implemented a perioperative guideline for obstructive sleep apnea (OSA), comprising a preoperative screening tool (BOSTN) and clinical management pathways. OSA was suspected with 2 or more of the following: body mass index ≥30 kg/m2, observed apnea, loud snoring, daytime tiredness, and neck circumference ≥16.5 inches in women or ≥ 17.5 inches in men. The primary objective of this study was to assess the association between high BOSTN scores and the requirement of invasive mechanical ventilation after surgery. METHODS: In this hospital registry study, 169,662 noncardiac surgical cases performed at Beth Israel Deaconess Medical Center (BIDMC), Boston, MA, between May 2008 and September 2017 were analyzed. We assessed the association between a high BOSTN Score (score ≥2) and the primary outcome of requirement of invasive mechanical ventilation within 7 days after surgery using multivariable logistic regression adjusted for patient-specific factors and case-specific surgical and anesthesiological confounders. Patients with a BOSTN Score ≥2 were assumed to have a high likelihood of suffering from OSA. Key secondary outcome was postoperative desaturation, defined as a peripheral oxygen saturation measurement <90% within 10 minutes of extubation. RESULTS: Invasive mechanical ventilation within 7 days of surgery was necessary in 3170 (2.3%) low-risk cases (BOSTN Score <2) and 664 (2.1%) high-risk cases (BOSTN Score ≥2). A score ≥2 was associated with significantly lower odds of requiring postoperative invasive ventilation (adjusted odds ratio [aOR], 0.89; 95% confidence interval [CI], 0.80–0.98; P = .017), but with an increased risk of postextubation desaturation (aOR, 1.34; 99.3% CI, 1.21–1.48; P < .001). Patients with a score ≥2 were hospitalized for an average of 3.71 days after surgery, compared to 4.27 days with a score <2 (adjusted incidence rate ratio [aIRR], 0.87; 99.3% CI, 0.84–0.91; P < .001). CONCLUSIONS: Patients at high risk of OSA required postoperative mechanical ventilation less frequently, had higher odds of postoperative desaturation, and were hospitalized for shorter periods of time. Accepted for publication May 14, 2019. Funding: M.E. receives unrestricted funds from philanthropic donors Jeffrey and Judy Buzen. E.S. receives departmental funding from the Department of Anesthesia, Critical Care and Pain Medicine at Beth Israel Deaconess Medical Center, Boston. All other authors have no financial disclosures. Conflicts of Interest: See Disclosures at the end of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.anesthesia-analgesia.org). D. Raub and P. Santer contributed equally and share first authorship. Reprints will not be available from the authors. Address correspondence to Eswar Sundar, MD, Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215. Address e-mail to esundar@bidmc.harvard.edu. © 2019 International Anesthesia Research Society

Delivery Hospital Characteristics and Postpartum Maternal Mortality: A National Case–Control Study in France BACKGROUND: The variability in resources for managing critical events among maternity hospitals may impact maternal safety. Our main objective was to assess the risk of postpartum maternal death according to hospitals' organizational characteristics. A secondary objective aimed to assess the specific risk of death due to postpartum hemorrhage (PPH). METHODS: This national population-based case–control study included all 2007–2009 postpartum maternal deaths from the national confidential enquiry (n= 147 cases) and a 2010 national representative sample of parturients (n = 14,639 controls). To adjust for referral bias, cases were classified by time when the condition/complication responsible for the death occurred: postpartum maternal deaths due to conditions present before delivery (n = 66) or during or after delivery (n = 81). Characteristics of delivery hospitals included 24/7 on-site availability of an anesthesiologist and an obstetrician, level of perinatal care, number of deliveries annually, and their teaching and profit status. In teaching and other nonprofit hospitals in France, obstetric care is organized on the principle of collective team-based management, while in for-profit hospitals, this organization is based mostly on that of "one woman–one doctor." Logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for postpartum maternal death. RESULTS: The risk of maternal death from prepartum conditions was lower for women who gave birth in for-profit compared with teaching hospitals (aOR, 0.3; 95% CI, 0.1–0.8; p = .02) and in hospitals with <1500 vs ≥1500 annual deliveries (aOR, 0.4; 95% CI, 0.1–0.9; P = .02). Conversely, the risk of postpartum maternal death from complications occurring during or after delivery was higher for women who delivered in for-profit compared with teaching hospitals (aOR, 2.8; 95% CI, 1.3–6.0; P = .009), as was the risk of death from PPH in for-profit versus nonprofit hospitals (aOR, 2.8; 95% CI, 1.2–6.5; P = .019). CONCLUSIONS: After adjustment for the referral bias related to prepartum morbidity, the risk of postpartum maternal mortality in France differs according to the hospital's organizational characteristics. Accepted for publication May 10, 2019. Funding: This work was funded by the French Institute for Public Health Research (IReSP). The French confidential enquiry into maternal deaths is funded by the French Institute for Public Health Surveillance (InVS) and the French National Institute of Health and Medical Research (Inserm). The French National Perinatal Survey was funded by the Ministry of Health. The French National Perinatal Survey was funded by the Ministry of Health. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.anesthesia-analgesia.org). A full list of contributors can be found at the end of the article. Reprints will not be available from the authors. Address correspondence to Monica Saucedo, MD, PhD, Inserm UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team (EPOPé), Centre for Epidemiology and Statistics Sorbonne Paris Cité (CRESS), DHU Risks in Pregnancy, Paris Descartes University, Maternité Port-Royal 6ème étage, 53 Avenue de l'Observatoire, 75014 Paris, France. Address e-mail to monica.saucedo@inserm.fr. © 2019 International Anesthesia Research Society

Functional MRI: Basic Principles and Emerging Clinical Applications for Anesthesiology and the Neurological Sciences No abstract available

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com