Assessment of Fluid Responsiveness in Prone Neurosurgical Patients Undergoing Protective Ventilation: Role of Dynamic Indices, Tidal Volume Challenge, and End-Expiratory Occlusion Test BACKGROUND: In patients in the prone position, the reliability of pulse pressure variation and stroke volume variation (PPV and SVV) and the use of functional hemodynamic tests to predict fluid responsiveness have not previously been established. Perioperatively, in this setting, optimizing fluid management can be challenging, and fluid overload is associated with both intraoperative and postoperative complications. We designed this study to assess the sensitivity and specificity of baseline PPV and SVV, the tidal volume (VT) challenge (VTC) and the end-expiratory occlusion test (EEOT) in predicting fluid responsiveness during elective spinal surgery. METHODS: The study protocol was started during a period of intraoperative hemodynamic stability after prone positioning and before the administration of any vasopressor: (1) at baseline, the controlled ventilation was set at 6 mL/kg of predicted body weight (PBW) (T0); (2) patients underwent the first EEOT (EEOT6) by interrupting the mechanical ventilation for 30 seconds; (3) the ventilation was set again at 6 mL/kg PBW for 1 minute (T1); (4) the VTC was applied by increasing the VT up to 8 mL/kg PBW for 1 minute; (5) the ventilation was kept at 8 mL/kg PBW for 1 minute (T2); (6) a second EEOT (EEOT8) was performed; (7) the VT was reduced back to 6 mL/kg PBW for 1 minute (T3); (8) a fluid challenge of 250 mL of Ringer’s solution was infused over 10 minutes. After each step, a complete set of hemodynamic measurements was recorded. RESULTS: Neither PPV and SVV values recorded at T3 nor the EEOT6 or the EEOT8 predicted fluid responsiveness. The change in PPV after VTC application predicted fluid responsiveness with an area under the curve of 0.96 (95% confidence interval, 0.87–1.00), showing a sensitivity of 95.2% and a specificity of 94.7%, using a cutoff increase of 12.2%. The change in SVV after VTC application predicted fluid responsiveness with an area under the curve 0.96 (95% confidence interval, 0.89–1.00) showing a sensitivity of 95.2% and a specificity of 94.7%, using a cutoff increase of 8.0%. A linear correlation between stroke volume index changes after fluid challenge administration and the changes in PPV and SVV after VTC application was observed (r = 0.71; P < .0001 and r = 0.68; P < .0001, respectively). CONCLUSIONS: In prone elective neurosurgical patients, the baseline values of PPV and SVV and the EEOT fail to predict fluid responsiveness, while the VTC is a very reliable functional hemodynamic test and could be helpful in guiding intraoperative fluid therapy. Accepted for publication September 18, 2019. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Trial registration: ACTRN12618000682246 (registration number at the Australian New Zealand Clinical Trials Registry). Reprints will not be available from the authors. Address correspondence to Antonio Messina, MD, PhD, Department of Anesthesia and Intensive Care Medicine, Humanitas Clinical and Research Center – IRCCS, Via Alessandro Manzoni, 56, 20089, Rozzano, Italy. Address e-mail to antonio.messina@humanitas.it. © 2019 International Anesthesia Research Society

A Population-Based Analysis of Intraoperative Cardiac Arrest in the United States BACKGROUND: A new billable code for intraoperative cardiac arrest was introduced with the International Classification of Diseases, Tenth Revision, classification system. Using a national administrative database, we performed a retrospective analysis of intraoperative cardiac arrest in the United States. METHODS: Hospital admissions involving patients ≥18 years of age who underwent operating room procedures in 2016 were identified using the National Inpatient Sample. The primary outcome was the incidence of intraoperative cardiac arrest. Secondary outcomes included total cost of admission, in-hospital mortality, length of stay, and identification of risk factors associated with intraoperative cardiac arrest. Clinical risk factors were evaluated with multivariable logistic regression models using sampling weights and adjustment for clustering by strata. RESULTS: Of 35,675,421 admissions in 2016 in the United States, 9,244,861 admissions were identified in patients ≥18 years of age who underwent at least one operating room procedure. An estimated 5230 hospital admissions involved intraoperative cardiac arrest, yielding an estimated incidence of 5.7 (95% confidence interval [CI], 5.3–6.0) per 10,000 hospital admissions. Admissions involving an intraoperative cardiac arrest had a 35.7% in-hospital mortality, compared with 1.3% for admissions without intraoperative cardiac arrest. Intraoperative cardiac arrest was associated with a 15.44-fold (95% CI, 12.74–18.70; P < .001) increase in the risk-adjusted odds of in-hospital mortality and an additional $13,184 (95% CI, 9600–16,769; P < .001) of total admission costs. Selected factors independently associated with increased risk-adjusted odds of intraoperative cardiac arrest included: black or missing race; cardiac, thoracic, or vascular surgery; congestive heart failure; pulmonary circulation disorders; peripheral vascular disease; end-stage renal disease; and fluid and electrolyte disorders. CONCLUSIONS: In this population-based study of intraoperative cardiac arrest in the United States, admissions involving an intraoperative cardiac arrest were rare but were associated with high in-hospital mortality. M. D. Willingham is currently affiliated with the Department of Anesthesiology, Division of Cardiothoracic Anesthesiology and Perioperative Medicine, Washington University in St Louis, St Louis, Missouri. Accepted for publication September 9, 2019. Funding: Support was provided primarily from institutional and/or departmental sources. M.A.F. reports support from a Society of Cardiovascular Anesthesiologists/International Anesthesia Research Society starter grant. 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). Reprints will not be available from the authors. Address correspondence to Vikram Fielding-Singh, MD, JD, Department of Anesthesiology & Perioperative Medicine, University of California, Los Angeles, 757 Westwood Plaza, Suite 3325, Los Angeles, CA 90095. Address e-mail to vfieldingsingh@mednet.ucla.edu. © 2019 International Anesthesia Research Society

Impact of the Addition of Examples to the American Society of Anesthesiologists Physical Status Classification System Examples of comorbidities for the widely used American Society of Anesthesiologists physical status (ASA-PS) classification system were developed and approved in 2014. We conducted a retrospective cohort study of patients with 4 comorbidities included in the examples as warranting a specific minimum ASA-PS class. For each comorbidity subgroup, we used interrupted time-series models to compare ASA-PS underclassification for the periods before (2011–2014) and after (2015–2017) the introduction of examples. Rates of underclassification ranged from 4.8% to 38.7%. We observed no evidence of a significant impact on ASA-PS classification with the introduction of examples in 2014. Accepted for publication September 11, 2019. M. D. Willingham is currently affiliated with the Division of Cardiothoracic Anesthesiology and Perioperative Medicine, Department of Anesthesiology, Washington University in St Louis, St Louis, Missouri. Funding: Institutional and/or departmental. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Vikram Fielding-Singh, MD, JD, Department of Anesthesiology & Perioperative Medicine, University of California, Los Angeles, 757 Westwood Plaza, Suite 3325, Los Angeles, CA 90095. Address e-mail to vfieldingsingh@mednet.ucla.edu. © 2019 International Anesthesia Research Society

Clinical Examination Skills in the Adult Critically Ill Patient No abstract available

The Perioperative Neurocognitive Disorders No abstract available

Anesthesia With and Without Nitrous Oxide and Long-term Cognitive Trajectories in Older Adults BACKGROUND: We evaluated the hypothesis that the rate of postoperative decline in global cognition is greater in older adults exposed to general anesthesia with nitrous oxide (N2O) compared to general anesthesia without N2O. METHODS: Longitudinal measures of cognitive function were analyzed in nondemented adults, 70–91 years of age, enrolled in the Mayo Clinic Study of Aging. Linear mixed-effects models with time-varying covariates assessed the relationship between exposure to surgery with general anesthesia (surgery/GA) with or without N2O and the rate of long-term cognitive changes. Global cognition and domain-specific cognitive outcomes were defined using z scores, which measure how far an observation is, in standard deviations, from the unimpaired population mean. RESULTS: The analysis included 1819 participants: 280 exposed to GA without N2O following enrollment and before censoring during follow-up (median [interquartile range {IQR}] follow-up of 5.4 [3.9–7.9] years); 256 exposed to GA with N2O (follow-up 5.6 [4.0–7.9] years); and 1283 not exposed to surgery/GA (follow-up 4.1 [2.5–6.4] years). The slope of the global cognitive z score was significantly more negative following exposure to surgery/GA after enrollment (change in slope of −0.062 [95% confidence interval {CI}, −0.085 to −0.039] for GA without N2O, and −0.058 [95% CI, −0.080 to −0.035] for GA with N2O, both P < .001). The change in slope following exposure to surgery/GA did not differ between those exposed to anesthesia without versus with N2O (estimated difference −0.004 [95% CI, −0.035 to 0.026], P = .783). CONCLUSIONS: Exposure to surgery/GA is associated with a small, but statistically significant decline in cognitive z scores. Cognitive decline did not differ between anesthetics with and without N2O. This finding provides evidence that the use of N2O in older adults does not need to be avoided because of concerns related to decline in cognition. Accepted for publication September 10, 2019. Funding: This study was supported by National Institutes of Health (NIH) grants P50 AG016574 and U01 AG006786 (R.C.P.); by the Robert H. and Clarice Smith and Abigail van Buren Alzheimer’s Disease Research Program; the Rochester Epidemiology Project (R01 AG034676, principal investigators Walter A. Rocca, MD, and Jennifer St. Sauver, PhD); and the Mayo Clinic Center for Translational Sciences Activities (CTSA) grant No. UL1 TR000135 from the National Center for Advancing Translational Sciences (NCATS). The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. Financial support for statistical analyses was provided by the Mayo Clinic Department of Anesthesiology. 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). Reprints will not be available from the authors. Address correspondence to Juraj Sprung, MD, PhD, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905. Address e-mail to sprung.juraj@mayo.edu. © 2019 International Anesthesia Research Society

Pathophysiological Response to Trauma-Induced Coagulopathy: A Comprehensive Review Hypercoagulability can occur after severe tissue injury, that is likely related to tissue factor exposure and impaired endothelial release of tissue plasminogen activator (tPA). In contrast, when shock and hypoperfusion occur, activation of the protein C pathway and endothelial tPA release induce a shift from a procoagulant to a hypocoagulable and hyperfibrinolytic state with a high risk of bleeding. Both thrombotic and bleeding phenotypes are associated with increased mortality and are influenced by the extent and severity of tissue injury and degree of hemorrhagic shock. Response to trauma is a complex, dynamic process in which risk can shift from bleeding to thrombosis depending on the injury pattern, hemostatic treatment, individual responses, genetic predisposition, and comorbidities. Based on this body of knowledge, we will review and consider future directions for the management of severely injured trauma patients. Accepted for publication September 10, 2019. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Patricia Duque, MD, PhD, Department of Anesthesiology and Intensive Care Medicine, Gregorio Marañon Hospital, Dr Esquerdo 46, 28007, Madrid, Spain. Address e-mail to patriduque@gmail.com. © 2019 International Anesthesia Research Society

In Response No abstract available

Preoperative Optimization: A Continued Call to Action No abstract available

Pennywise and a Pound Foolish: The Advantage of Dantrolene Nanosuspension (Ryanodex) in the Treatment of Malignant Hyperthermia No abstract available