Etomidate versus ketamine for emergency endotracheal intubation: a randomized clinical trial.

PURPOSE: Etomidate and ketamine are hemodynamically stable induction agents often used to sedate critically ill patients during emergency endotracheal intubation. In 2015, quality improvement data from our hospital suggested a survival benefit at Day 7 from avoidance of etomidate in critically ill patients during emergency intubation. In this clinical trial, we hypothesized that randomization to ketamine instead of etomidate would be associated with Day 7 survival after emergency endotracheal intubation. METHODS: A prospective, randomized, open-label, parallel assignment, single-center clinical trial performed by an anesthesiology-based Airway Team under emergent circumstances at one high-volume medical center in the United States. 801 critically ill patients requiring emergency intubation were randomly assigned 1:1 by computer-generated, pre-randomized sealed envelopes to receive etomidate (0.2-0.3 mg/kg, n = 400) or ketamine (1-2 mg/kg, n = 401) for sedation prior to intubation. The pre-specified primary endpoint of the trial was Day 7 survival. Secondary endpoints included Day 28 survival. RESULTS: Of the 801 enrolled patients, 396 were analyzed in the etomidate arm, and 395 in the ketamine arm. Day 7 survival was significantly lower in the etomidate arm than in the ketamine arm (77.3% versus 85.1%, difference - 7.8, 95% confidence interval - 13, - 2.4, p = 0.005). Day 28 survival rates for the two groups were not significantly different (etomidate 64.1%, ketamine 66.8%, difference - 2.7, 95% confidence interval - 9.3, 3.9, p = 0.294). CONCLUSION: While the primary outcome of Day 7 survival was greater in patients randomized to ketamine, there was no significant difference in survival by Day 28.

Proton reirradiation for recurrent or new primary breast cancer in the setting of prior breast irradiation.

BACKGROUND AND PURPOSE: Late local recurrences and second primary breast cancers are increasingly common. Proton beam therapy (PBT) reirradiation (reRT) may allow safer delivery of a second definitive radiotherapy (RT) course. We analyzed outcomes of patients with recurrent or new primary breast cancer who underwent reRT. MATERIALS AND METHODS: In an IRB-approved retrospective study, patient/tumor characteristics, treatment parameters, outcomes, and toxicities were collected for all consecutive patients with recurrent or new primary non-metastatic breast cancer previously treated with breast or chest wall RT who underwent PBT reRT. RESULTS: Forty-six patients received reRT using uniform (70%) or pencil beam (30%) scanning PBT. Median first RT, reRT, and cumulative doses were 60 Gy (range 45-66 Gy), 50.4 Gy(RBE) (40-66.6 Gy(RBE)), and 110 Gy(RBE) (96.6-169.4 Gy(RBE)), respectively. Median follow-up was 21 months. There were no local or regional recurrences; 17% developed distant recurrence. Two-year DMFS and OS were 92.0% and 93.6%, respectively. Nine of 13 (69.2%) patients who underwent implant or flap reconstruction developed capsular contracture, 3 (23.1%) requiring surgical intervention. One (7.7%) patient developed grade 3 breast pain requiring mastectomy after breast conserving surgery. No acute or late grade 4-5 toxicities were seen. Increased body mass index (BMI) was protective of grade ≥ 2 acute toxicity (OR = 0.84, 95%CI = 0.70-1.00). CONCLUSION: In the largest series to date of PBT reRT for breast cancer recurrence or new primary after prior definitive breast or chest wall RT, excellent locoregional control and few high-grade toxicities were encountered. PBT reRT may provide a relatively safe and highly effective salvage option. Additional patients and follow-up are needed to correlate composite normal tissue doses with toxicities and assess long-term outcomes.

A Positive Cocaine Urine Toxicology Test and the Effect on Intraoperative Hemodynamics Under General Anesthesia.

BACKGROUND: Cocaine has a short biological half-life, but inactive urine metabolites may be detectable for a week following use. It is unclear if patients who test positive for cocaine but have a normal electrocardiogram and vital signs have a greater percentage of hemodynamic events intraoperatively. METHODS: A total of 328 patients with a history of cocaine use who were scheduled for elective noncardiac surgery under general anesthesia were enrolled. Patients were categorized into cocaine-positive versus cocaine-negative groups based on the results of their urine cocaine toxicology test. The primary aim of this study was to evaluate whether asymptomatic cocaine-positive patients had similar percentages of intraoperative hemodynamic events, defined as (1) a mean arterial blood pressure (MAP) of <65 or >105 mm Hg and (2) a heart rate (HR) of <50 or >100 beats per minute (bpm) compared to cocaine-negative patients. The study was powered to assess if the 2 groups had an equivalent mean percent of intraoperative hemodynamic events within specific limits using an equivalence test of means consisting of 2 one-sided tests. RESULTS: The cocaine-positive group had a blood pressure (BP) that was outside the set limits 19.4% (standard deviation [SD] 17.7%) of the time versus 23.1% (SD 17.7%) in the cocaine-negative group (95% confidence interval [CI], 0.5-7.0). The cocaine-positive group had a HR outside the set limits 9.6% (SD 16.2%) of the time versus 8.2% (SD 14.9%) in the cocaine-negative group (95% CI, 4.3-1.5). Adjusted for age, sex, body mass index (BMI), smoking status, and the presence of comorbid hypertension, renal disease, and psychiatric illness, the cocaine-positive and cocaine-negative patients were similar within a 7.5% margin of equivalence for MAP data (ß coefficient = 2%, P = .003, CI, 2-6) and within a 5% margin of equivalence for HR data (ß coefficient = 0.2%, P < .001, CI, 4-3). CONCLUSIONS: Asymptomatic cocaine-positive patients undergoing elective noncardiac surgery under general anesthesia have similar percentages of intraoperative hemodynamic events compared to cocaine-negative patients.

Temporal Lobe Necrosis in Head and Neck Cancer Patients after Proton Therapy to the Skull Base.

PURPOSE: To demonstrate temporal lobe necrosis (TLN) rate and clinical/dose-volume factors associated with TLN in radiation-naïve patients with head and neck cancer treated with proton therapy where the field of radiation involved the skull base. MATERIALS AND METHODS: Medical records and dosimetric data for radiation-naïve patients with head and neck cancer receiving proton therapy to the skull base were retrospectively reviewed. Patients with <3 months of follow-up, receiving <45 GyRBE or nonconventional fractionation, and/or no follow-up magnetic resonance imaging (MRI) were excluded. TLN was determined using MRI and graded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Clinical (gender, age, comorbidities, concurrent chemotherapy, smoking, radiation techniques) and dose-volume parameters were analyzed for TLN correlation. The receiver operating characteristic curve and area under the curve (AUC) were performed to determine the cutoff points of significant dose-volume parameters. RESULTS: Between 2013 and 2019, 234 patients were included. The median follow-up time was 22.5 months (range = 3.2-69.3). Overall TLN rates of any grade, ≥ grade 2, and ≥ grade 3 were 5.6% (N = 13), 2.1%, and 0.9%, respectively. The estimated 2-year TLN rate was 4.6%, and the 2-year rate of any brain necrosis was 6.8%. The median time to TLN was 20.9 months from proton completion. Absolute volume receiving 40, 50, 60, and 70 GyRBE (absolute volume [aV]); mean and maximum dose received by the temporal lobe; and dose to the 0.5, 1, and 2 cm3 volume receiving the maximum dose (D0.5cm3, D1cm3, and D2cm3, respectively) of the temporal lobe were associated with greater TLN risk while clinical parameters showed no correlation. Among volume parameters, aV50 gave maximum AUC (0.921), and D2cm3 gave the highest AUC (0.935) among dose parameters. The 11-cm3 cutoff value for aV50 and 62 GyRBE for D2cm3 showed maximum specificity and sensitivity. CONCLUSION: The estimated 2-year TLN rate was 4.6% with a low rate of toxicities ≥grade 3; aV50 ≤11 cm3, D2cm3 ≤62 GyRBE and other cutoff values are suggested as constraints in proton therapy planning to minimize the risk of any grade TLN. Patients whose temporal lobe(s) unavoidably receive higher doses than these thresholds should be carefully followed with MRI after proton therapy.

Sugammadex versus neostigmine for reversal of rocuronium-induced neuromuscular blockade: A randomized, double-blinded study of thoracic surgical patients evaluating hypoxic episodes in the early postoperative period.

STUDY OBJECTIVE: This objective of this study was to determine if reversal of rocuronium-induced neuromuscular blockade with sugammadex versus neostigmine results in a decreased number of hypoxic episodes in the early postoperative period in patients undergoing thoracic surgery with single lung ventilation. DESIGN: Single-center, randomized, double-blind, two-arm clinical trial. SETTING: Operating room and postanesthesia care unit. PATIENTS: 92 subjects aged ≥18, American Society of Anesthesiologists physical status II-IV, and undergoing a thoracic operation necessitating single lung ventilation. INTERVENTIONS: Subjects received either 2 mg/kg sugammadex or 50 µg/kg neostigmine with 8 µg/kg glycopyrrolate for reversal of moderate neuromuscular blockade. MEASUREMENTS: For the first 90 min postoperatively, all episodes of hypoxia were recorded. Neuromuscular monitoring was performed with acceleromyography (TOF-Watch® SX) and the train of four (TOF) was recorded at 2, 5, 10, and 15 min after administration of the neuromuscular reversal agent. MAIN RESULTS: Subjects who received neostigmine had a median of 1 episode (interquartile range IQR: 0-2.2) of hypoxia versus subjects who received sugammadex who had a median of 0 episodes (IQR: 0-1) (p = 0.009). The mean time to recovery of TOF ≥ 0.9 was significantly faster with sugammadex at 10 min (95% confidence interval CI: 5-15) compared with neostigmine at 40 min (95% CI: 15-53) (p < 0.001). CONCLUSIONS: In thoracic surgical patients necessitating single lung ventilation, sugammadex provides faster reversal of moderate neuromuscular blockade and results in a decreased number of postoperative hypoxic episodes compared with neostigmine.

Outcomes and toxicities of definitive radiotherapy and reirradiation using 3-dimensional conformal or intensity-modulated (pencil beam) proton therapy for patients with nasal cavity and paranasal sinus malignancies.

BACKGROUND: Proton therapy (PT) improves outcomes in patients with nasal cavity (NC) and paranasal sinus (PNS) cancers. Herein, the authors have reported to their knowledge the largest series to date using intensity-modulated proton therapy (IMPT) in the treatment of these patients. METHODS: Between 2013 and 2018, a total of 86 consecutive patients (68 of whom were radiation-naive and 18 of whom were reirradiated) received PT to median doses of 70 grays and 67 grays relative biological effectiveness, respectively. Approximately 53% received IMPT. RESULTS: The median follow-up was 23.4 months (range, 1.7-69.3 months) for all patients and 28.1 months (range, 2.3-69.3 months) for surviving patients. The 2-year local control (LC), distant control, disease-free survival, and overall survival rates were 83%, 84%, 74%, and 81%, respectively, for radiation-naive patients and 77%, 80%, 54%, and 66%, respectively for reirradiated patients. Among radiation-naive patients, when compared with 3-dimensional conformal proton technique, IMPT significantly improved LC (91% vs 72%; P < .01) and independently predicted LC (hazard ratio, 0.14; P = .01). Sixteen radiation-naive patients (24%) experienced acute grade 3 toxicities; 4 (6%) experienced late grade 3 toxicities (osteoradionecrosis, vision loss, soft-tissue necrosis, and soft tissue fibrosis) (grading was performed according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 5.0]). Slightly inferior LC was noted for patients undergoing reirradiation with higher complications: 11% experienced late grade 3 toxicities (facial pain and brain necrosis). Patients treated with reirradiation had more grade 1 to 2 radionecrosis than radiation-naive patients (brain: 33% vs 7% and osteoradionecrosis: 17% vs 3%). CONCLUSIONS: PT achieved remarkable LC for patients with nasal cavity and paranasal sinus cancers with lower grade 3 toxicities relative to historical reports. IMPT has the potential to improve the therapeutic ratio in these malignancies and is worthy of further investigation.

Apneic Oxygenation During Prolonged Laryngoscopy in Obese Patients: a Randomized, Double-Blinded, Controlled Trial of Nasal Cannula Oxygen Administration.

BACKGROUND: Obese patients have a propensity to desaturate during induction of general anesthesia secondary to their reduced functional residual capacity and increased oxygen consumption. Apneic oxygenation can provide supplemental oxygen to the alveoli, even in the absence of ventilation, during attempts to secure the airway. In this study, we hypothesized that oxygen administration through a nasopharyngeal airway and standard nasal cannula during a simulated prolonged laryngoscopy would significantly prolong the safe apneic duration in obese patients. METHODS: One hundred thirty-five obese patients undergoing non-emergent surgery requiring general anesthesia were randomized to either the control group or to receive apneic oxygenation with air versus oxygen. All patients underwent a standard intravenous induction. For patients randomized to receive apneic oxygenation, a nasopharyngeal airway and standard nasal cannula were inserted. A simulated prolonged laryngoscopy was performed to determine the duration of the safe apneic period, defined as the beginning of laryngoscopy until the peripheral oxygen saturation (SpO2) reached 95%. RESULTS: The oxygen group had a median safe apneic duration that was 103 s longer than the control group. The lowest mean SpO2 value during the induction period was 3.8% higher in the oxygen group compared to the control group. Following intubation, patients in the oxygen group had a mean end tidal carbon dioxide (ETCO2) level that was 3.0 mmHg higher than patients in the control group. CONCLUSIONS: In obese patients, oxygen insufflation at 15 L/min through a nasopharyngeal airway and standard nasal cannula can significantly increase the safe apneic duration during induction of anesthesia.

Recent cocaine use and the incidence of hemodynamic events during general anesthesia: A retrospective cohort study.

STUDY OBJECTIVE: To evaluate the intraoperative hemodynamics and medication requirements of cocaine-positive patients compared to matched cocaine-negative controls. DESIGN: Retrospective cohort study. SETTING: Public county hospital. PATIENTS: 821 patients undergoing general anesthesia. MEASUREMENTS: Incidence of hemodynamic events, defined by a mean arterial pressure of <65 mmHg or >105 mmHg or a heart rate of <50 beats per minute or >100 beats per minute. MAIN RESULTS: Cocaine-positive patients did not experience a higher incidence of hemodynamic events when compared with matched cocaine-negative patients. Cocaine-positive patients were not more likely to be administered vasopressors intraoperatively but did receive more anti-hypertensive agents. The minimum alveolar concentration of anesthetics used was similar between the two groups. Anesthesia duration, length of stay, and in-hospital mortality did not significantly differ between the two cohorts. CONCLUSIONS: Cocaine-positive patients did not demonstrate more intraoperative hemodynamic events or adverse short-term outcomes as compared to matched cocaine-negative controls.

The influence of morbid obesity on difficult intubation and difficult mask ventilation.

PURPOSE: To determine the influence of morbid obesity on the incidence of difficult mask ventilation and difficult intubation. METHODS: Over a 6-year period, all tracheal intubations in the operating room of a large tertiary teaching hospital were analyzed. A modified version of the intubation difficulty scale (mIDS) was used to define easy versus difficult intubation, where a score of two or greater was defined as difficult intubation. Difficult mask ventilation was defined as the use of one or more adjuncts to achieve successful mask ventilation. RESULTS: Of 45,447 analyzed cases, 1893 (4.2%) were classified as difficult intubations. Morbidly obese patients were not more likely to have difficult intubation [Odds Ratio (OR) = 1.131, 95% confidence interval (CI): 0.958, 1.334, p = 0.146]. Factors that were associated with difficult intubation included patient age > 46 years, male sex, Mallampati 3-4, thyromental distance < 6 cm, and the presence of intact dentition. Of 37,016 cases in which mask ventilation was attempted, 1069 (2.9%) were difficult. Morbidly obese patients were more likely to have difficult mask ventilation (OR = 3.785, 95% CI: 3.188, 4.493, p < 0.0001). Other factors associated with difficult mask ventilation included patient age > 46 years, male sex, Mallampati 3-4, and a history of obstructive sleep apnea. Having intact dentition decreased the likelihood of difficult mask ventilation. CONCLUSION: Morbidly obese patients do not have a higher incidence of difficult intubation compared to non-morbidly obese patients. However, they have a significantly higher incidence of difficult mask ventilation. Other factors that are predictive of both difficult mask ventilation and difficult intubation include age > 46 years, male sex, and Mallampati 3-4.

Machine Learning, Sentiment Analysis, and Tweets: An Examination of Alzheimer's Disease Stigma on Twitter.

OBJECTIVES: Social scientists need practical methods for harnessing large, publicly available datasets that inform the social context of aging. We describe our development of a semi-automated text coding method and use a content analysis of Alzheimer's disease (AD) and dementia portrayal on Twitter to demonstrate its use. The approach improves feasibility of examining large publicly available datasets. METHOD: Machine learning techniques modeled stigmatization expressed in 31,150 AD-related tweets collected via Twitter's search API based on 9 AD-related keywords. Two researchers manually coded 311 random tweets on 6 dimensions. This input from 1% of the dataset was used to train a classifier against the tweet text and code the remaining 99% of the dataset. RESULTS: Our automated process identified that 21.13% of the AD-related tweets used AD-related keywords to perpetuate public stigma, which could impact stereotypes and negative expectations for individuals with the disease and increase "excess disability". DISCUSSION: This technique could be applied to questions in social gerontology related to how social media outlets reflect and shape attitudes bearing on other developmental outcomes. Recommendations for the collection and analysis of large Twitter datasets are discussed.

Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) are stigmatizing illnesses characterized by cognitive difficulties, post-exertional malaise, unrefreshing sleep, and other symptoms. Patients are often incapacitated and stigmatized as having a psychological disorder. The Chronic Fatigue Attitudes Test (CAT) assesses stigmatizing views toward individuals with Chronic Fatigue Syndrome, however, there is little research examining factors that may account for variation in stigmatizing attitudes toward this group. We examined CAT scores among college age research volunteers (N = 90), hypothesizing that exposure to information about ME and CFS as a result of volunteering on a ME and CFS-related research project would be associated with less stigmatizing attitudes compared to volunteers on unrelated projects. Findings indicated that ME and CFS research volunteers expressed less stigmatizing attitudes. Educational efforts aiming to disseminate accurate information about ME and CFS may mitigate stigma and the experience of stigma among individuals with ME and CFS.

Improving the quality of the operating room to intensive care unit handover at an urban teaching hospital through a bundled intervention.

STUDY OBJECTIVE: To evaluate the efficacy of a bundled intervention to improve the quality of the operating room to intensive care unit (ICU) clinical handover. DESIGN: Prospective, interventional study. SETTING: An urban, public teaching hospital with more than 1500 direct postoperative ICU admissions each year. INTERVENTIONS: A bundled intervention to include the addition of a direct anesthesia provider to ICU nurse telephone report, a mnemonic to standardize the handover process, and improved template for postoperative documentation by the anesthesia team. MEASUREMENTS: Preintervention (baseline) and postintervention survey data were solicited from key stakeholders, which included anesthesia providers and ICU nursing staff. MAIN RESULTS: Anesthesia provider and ICU nursing staff satisfaction levels rose significantly following implementation of the bundled intervention. In addition, perceived effectiveness of the handover process and note increased significantly. The satisfaction level of the ICU nurses with respect to the phone report received before patient arrival in the ICU nearly doubled. CONCLUSIONS: The implementation of a bundled handover intervention was associated with increased stakeholder satisfaction as well as a perception of increased efficacy and quality of the overall handover process and postoperative anesthesia documentation.

Successful near-term pregnancy outcome after repair of a dissecting thoracic aortic aneurysm at 14 weeks gestation.

PURPOSE: We report the anesthetic management for a scheduled Cesarean section of a 29-yr-old female who previously had a repair of her dissecting thoracic aortic aneurysm during the 14th week of her pregnancy. CLINICAL FEATURES: A 29-yr-old female with a history of hypertension and previously diagnosed aortic dissection secondary to suspected Marfan's syndrome, presented to our institution for the first time after she became pregnant. A transesophageal echocardiogram revealed a dissecting aortic aneurysm greater than 8 cm in diameter beginning distal to the left subclavian artery and extending into the descending thoracic aorta. The patient was counseled in great detail about the risk of rupture with continuing pregnancy. She refused termination and chose elective repair of the aneurysm, with continuation of the pregnancy. Partial repair of the thoracic aneurysm was undertaken when the pregnancy was 13(5/7) weeks by ultrasound dates. She was subsequently maintained on labetolol and hydralazine for blood pressure control. A decision was made to proceed with a Cesarean section at 32 weeks. After placement of a radial artery catheter and two large peripheral iv catheters, she received a of 7 and 7 at one and five minutes was delivered. CONCLUSIONS: Aortic dissection in pregnancy may have catastrophic results. Undoubtedly, it presents unique challenges for anesthetic and obstetrical management. With appropriate care and surgical correction of the dissecting aneurysm early in pregnancy, a successful outcome for the pregnancy was possible.