Long Interspersed Nuclear Element-1 Analytes in Extracellular Vesicles as Tools for Molecular Diagnostics of Non-Small Cell Lung Cancer.

Aberrant expression of the oncogenic retrotransposon LINE-1 is a hallmark of various cancer types, including non-small cell lung cancers (NSCLCs). Here, we present proof-of-principle evidence that LINE-1 analytes in extracellular vesicles (EVs) serve as tools for molecular diagnostics of NSCLC, with LINE-1 status in tumor cells and tissues mirroring the LINE-1 mRNA and ORF1p cargos of EVs from lung cancer cell culture conditioned media or human plasma. The levels of LINE-1 analytes in plasma EVs from ostensibly healthy individuals were higher in females than males. While the profiles of LINE-1 mRNA and ORF1p in African Americans compared to Hispanics were not significantly different, African Americans showed slightly higher ORF1p content, and 2-3 times greater ranges of LINE-1 values compared to Hispanics. Whole plasma ORF1p levels correlated with EV ORF1p levels, indicating that most of the circulating LINE-1 protein is contained within EVs. EV LINE-1 mRNA levels were elevated in patients with advanced cancer stages and in select patients with squamous cell carcinoma and metastatic tumors compared to adenocarcinomas. The observed EV LINE-1 mRNA profiles paralleled the patterns of ORF1p expression in NSCLC tissue sections suggesting that LINE-1 analytes in plasma EVs may serve to monitor the activity of LINE-1 retroelements in lung cancer.

A comparison of patient, intervention, comparison, outcome (PICO) to a new, alternative clinical question framework for search skills, search results, and self-efficacy: a randomized controlled trial.

OBJECTIVE: In educating students in the health professions about evidence-based practice, instructors and librarians typically use the patient, intervention, comparison, outcome (PICO) framework for asking clinical questions. A recent study proposed an alternative framework for the rehabilitation professions. The present study investigated the effectiveness of teaching the alternative framework in an educational setting. METHODS: A randomized controlled trial was conducted with students in occupational therapy (OT) and physical therapy (PT) to determine if the alternative framework for asking clinical questions was effective for identifying information needs and searching the literature. Participants were randomly allocated to a control or experimental group to receive ninety minutes of information literacy instruction from a librarian about formulating clinical questions and searching the literature using MEDLINE. The control group received instruction that included the PICO question framework, and the experimental group received instruction that included the alternative framework. RESULTS: There were no significant differences in search performance or search skills (strategy and clinical question formulation) between the two groups. Both the control and experimental groups demonstrated a modest but significant increase in information literacy self-efficacy after the instruction; however, there was no difference between the two groups. CONCLUSION: When taught in an information literacy session, the new, alternative framework is as effective as PICO when assessing OT and PT students' searching skills. Librarian-led workshops using either question formulation framework led to an increase in information literacy self-efficacy post-instruction.

Risk factors and outcomes of postoperative emergency response team activation: a matched case-control study.

OBJECTIVE: To determine patient and perioperative characteristics associated with unexpected postoperative clinical deterioration as determined for the need of a postoperative emergency response team (ERT) activation. DESIGN: Retrospective case-control study. SETTING: Tertiary academic hospital. PARTICIPANTS: Patients who underwent general anaesthesia discharged to regular wards between 1 January 2013 and 31 December 2015 and required ERT activation within 48 postoperative hours. Controls were matched based on age, sex and procedure. MAIN OUTCOME MEASURES: Baseline patient and perioperative characteristics were abstracted to develop a multiple logistic regression model to assess for potential associations for increased risk for postoperative ERT. RESULTS: Among 105 345 patients, 797 had ERT calls, with a rate of 7.6 (95% CI, 7.1-8.1) calls per 1000 anaesthetics (0.76%). Multiple logistic regression analysis showed the following risk factors for postoperative ERT: cardiovascular disease (odds ratio [OR], 1.61; 95% CI, 1.18-2.18), neurological disease (OR, 1.57; 95% CI, 1.11-2.22), preoperative gabapentin (OR, 1.60; 95% CI, 1.17-2.20), longer surgical duration (OR, 1.06; 95% CI, 1.02-1.11, per 30 min), emergency procedure (OR, 1.54; 95% CI, 1.09-2.18), and intraoperative use of colloids (OR, 1.50; 95% CI, 1.17-1.92). Compared with control participants, ERT patients had a longer hospital stay, a higher rate of admissions to critical care (55.5%), increased postoperative complications, and a higher 30-day mortality rate (OR, 3.36; 95% CI, 1.73-6.54). CONCLUSION: We identified several patient and procedural characteristics associated with increased likelihood of postoperative ERT activation. ERT intervention is a marker for increased rates of postoperative complications and death.

Oncologic Outcomes in Young Adults With Kidney Cancer Treated During the Targeted Therapy Era.

BACKGROUND: The objective of this study was to determine the outcomes of young adults with kidney cancer treated during the targeted therapy era and evaluate the impact of young age on survival. MATERIALS AND METHODS: We reviewed the records from 445 patients younger than 55 years with kidney cancer at a single institution from 2006 to 2017. Overall survival (OS) and recurrence-free survival were estimated with the Kaplan-Meier method and log-rank test. Cox proportional hazards regression was used to determine the impact of clinical and pathologic variables on all-cause mortality. RESULTS: Overall, 104 (23%) patients 40 years or younger were compared with 341 (77%) patients who were 41 to 55 years old. Younger patients presented with more advanced stages of the disease, including metastasis at diagnosis, positive lymph nodes, venous tumor thrombus and had more non-clear cell tumors (54% vs. 30%; P < .001). Young adults had significantly worse OS at 2 and 5 years (67% vs. 82% and 53% vs. 69%, respectively). Younger patients with metastatic disease received targeted agents less often compared with the older group (64% vs. 75%). There was no difference in recurrence-free survival across patients with localized disease. Independent prognostic factors associated with increased mortality were metastasis at diagnosis, pT2 or greater, and age younger than 40 years (hazard ratio, 1.65; 95% confidence interval, 1.0-2.6; P = .03). CONCLUSION: Patients younger than 40 years with kidney tumors treated during the targeted therapy era have worse OS compared with older adults. Young age is an independent predictor of mortality.

Robot-assisted extended pelvic lymph node dissection in prostate cancer. When and how?

OBJECTIVE: To review the literature evaluating the role of the extended pelvic lymph node dissectione PLND during robot assisted radical prostatectomy (RARP) in the management of PCa patients, as well as the preoperative clinic pathologic factors that predict lymph node metastases (LNM). The technique and current outcomes of robotic ePLND will be presented. METHODS: Medline®/Pubmed® were searched up to august 2018 to find comparative studies of different anatomic limits of pelvic lymph node dissection (PLND) during RARP, open or pure laparoscopic surgery that reported number of nodes retrieved, oncologic outcomes and complications. The search was complemented to identify studies that evaluated diagnostic images and factors that predict LNM. Overall, 44 articles were included for full text review. RESULTS: There is not an imaging technique with an acceptable performance to select patients for PLND, the decision to perform a PLND is based on clinical characteristics described on validated nomograms. Median lymph node yield at RARP range from 5 to 21 depending on the extent of PLND, positivity rate of LN as high as 37% depending on the risk stratification of patients. Robot-assisted can be carried out to any extent with lymph node yields and safety concerns comparable to the open approach. CONCLUSION: Extended pelvic lymph node dissection is recommended to be performed at the time of RARP in intermediate and high-risk patients and cannot be replaced by other modalities. A benefit in terms of oncologic outcomes remains to be established. The robot assisted approach offers shorter length of hospital stay, lower transfusion rates and comparable outcomes compared to other surgical approaches.

ARTICULO SOLO EN INGLES.OBJETIVO: Revisar la literatura que evalúa  el papel de la linfadenectomía pélvica extendida  (LPe) durante la prostatectomía radical asistida por robot  (PRAR) en el manejo de pacientes con cáncer de próstata,  así como los factores clínico-patológicos preoperatorios  que predicen las metástasis ganglionares. Presentamos la técnica de LPe y sus resultados actuales.MÉTODOS: Se realizó una búsqueda bibliográfica en Medline®/Pubmed® hasta agosto 2018 para encontrar estudios comparativos de los diferentes límites anatómicos de la linfadenectomía pélvica duranteprostatectomía radical asistida por robot, abierta olaparoscópica que comunicaran número de ganglios,resultados oncológicos y complicaciones. La búsquedafue complementada para identificar estudios que evaluaran imágenes diagnósticas y factores predictivos demetástasis ganglionares. Finalmente, se incluyeron 44artículos. RESULTADOS: No hay una técnica de imagen que tengauna resolución aceptable para seleccionar pacientespara linfadenectomía. La decisión de practicar linfadenectomíase basa en las características clínicas descritasen nomogramas validados. La mediana del númerode ganglios obtenidos oscila entre 5 y 21 dependiendode la extensión de la linfadenectomía, y la tasa de gangliospositivos es tan alta como el 37% dependiendo dela estratificación del riesgo de los pacientes. La cirugíaasistida por robot puede realizarse con cualquier extensióncon un número de ganglios obtenidos y aspectosde seguridad comparables con el abordaje abierto. CONCLUSION: Se recomienda realizar la linfadenectomíapélvica extendida en el momento de la PRAR enpacientes de riesgo intermedio y alto y no puede reemplazarsepor otras modalidades. Sigue por establecerseun beneficio en términos de resultados oncológicos. Elabordaje asistido por robot ofrece estancias hospitalariasmás cortas, menores tasas de transfusión y resultadoscomparables en comparación con otros abordajesquirúrgicos.

Robot-assisted extended pelvic lymph node dissection in prostate cancer, when and how? / Linfadenectomía pélvica extendida en cáncer de próstata. ¿Cuándo y cómo?

Objective: To review the literature evaluating the role of the extended pelvic lymph node dissection ePLND during robot assisted radical prostatectomy (RARP) in the management of PCa patients, as well as the preoperative clinic pathologic factors that predict lymph node metastases (LNM). The technique and current outcomes of robotic ePLND will be presented. Methods: Medline(R)/Pubmed(R) were searched up to august 2018 to find comparative studies of different anatomic limits of pelvic lymph node dissection (PLND) during RARP, open or pure laparoscopic surgery that reported number of nodes retrieved, oncologic outcomes and complications. The search was complemented to identify studies that evaluated diagnostic images and factors that predict LNM. Overall, 44 articles were included for full text review. Results: There is not an imaging technique with an acceptable performance to select patients for PLND, the decision to perform a PLND is based on clinical characteristics described on validated nomograms. Median lymph node yield at RARP range from 5 to 21 depending on the extent of PLND, positivity rate of LN as high as 37% depending on the risk stratification of patients. Robot-assisted can be carried out to any extent with lymph node yields and safety concerns comparable to the open approach. CONCLUSION: Extended pelvic lymph node dissection is recommended to be performed at the time of RARP in intermediate and high-risk patients and cannot be replaced by other modalities. A benefit in terms of oncologic outcomes remains to be established. The robot assisted approach offers shorter length of hospital stay, lower transfusion rates and comparable outcomes compared to other surgical approaches

Objetivo: Revisar la literatura que evalúa el papel de la linfadenectomía pélvica extendida (LPe) durante la prostatectomía radical asistida por robot (PRAR) en el manejo de pacientes con cáncer de próstata, así como los factores clínico-patológicos preoperatorios que predicen las metástasis ganglionares. Presentamos la técnica de LPe y sus resultados actuales. Métodos: Se realizó una búsqueda bibliográfica en Medline(R)/Pubmed(R) hasta agosto 2018 para encontrar estudios comparativos de los diferentes límites anatómicos de la linfadenectomía pélvica durante prostatectomía radical asistida por robot, abierta o laparoscópica que comunicaran número de ganglios, resultados oncológicos y complicaciones. La búsqueda fue complementada para identificar estudios que evaluaran imágenes diagnósticas y factores predictivos de metástasis ganglionares. Finalmente, se incluyeron 44 artículos. Resultados: No hay una técnica de imagen que tenga una resolución aceptable para seleccionar pacientes para linfadenectomía. La decisión de practicar linfadenectomía se basa en las características clínicas descritas en nomogramas validados. La mediana del número de ganglios obtenidos oscila entre 5 y 21 dependiendo de la extensión de la linfadenectomía, y la tasa de ganglios positivos es tan alta como el 37% dependiendo de la estratificación del riesgo de los pacientes. La cirugía asistida por robot puede realizarse con cualquier extensión con un número de ganglios obtenidos y aspectos de seguridad comparables con el abordaje abierto. Conclusión: Se recomienda realizar la linfadenectomía pélvica extendida en el momento de la PRAR en pacientes de riesgo intermedio y alto y no puede reemplazarse por otras modalidades. Sigue por establecerse un beneficio en términos de resultados oncológicos. El abordaje asistido por robot ofrece estancias hospitalarias más cortas, menores tasas de transfusión y resultados comparables en comparación con otros abordajes quirúrgicos

Incidence of congenital diaphragmatic hernia in Olmsted County, Minnesota: a population-based study.

OBJECTIVE: The rate of congenital diaphragmatic hernia (CDH) varies, but most reports estimate the incidence to be less than three per 10,000 births. Our objective was to document the incidence of CDH in a geographically well-defined population using available resources for highly accurate incident case ascertainment. METHODS: We ascertained CDH cases in Olmsted County, Minnesota, United States of America, from 1981 through 2014 using resources of the Rochester Epidemiology Project. Overall and sex-specific incidence rates were calculated, and hospital survival was assessed. RESULTS: A total of 26 incident CDH cases were identified; the overall incidence of 3.6 (95% CI, 2.2-5.0) per 10,000 did not differ significantly over the 34-year study period (p = .28). The estimated incidence was 4.3 (95% CI, 2.2-6.5) for male infants and 2.9 (95% CI, 1.1-4.6) for female infants. The percentage of cases diagnosed prenatally was 33% from 1981 through 2000 and 50% from 2001 through 2014. The rate of survival to discharge in the two periods was 50% and 88%. CONCLUSION: The incidence of CDH in Olmsted County exceeds the majority of published rates, which most likely can be attributed to our comprehensive case ascertainment.

Low minute ventilation episodes during anesthesia recovery following intraperitoneal surgery as detected by a non-invasive respiratory volume monitor.

An electrical impedance-based noninvasive respiratory volume monitor (RVM) accurately reports minute volume, tidal volume and respiratory rate. Here we used the RVM to quantify the occurrence of and evaluate the ability of clinical factors to predict respiratory depression in the post-anesthesia care unit (PACU). RVM generated respiratory data were collected from spontaneously breathing patients following intraperitoneal surgeries under general anesthesia admitted to the PACU. Respiratory depression was defined as low minute ventilation episode (LMVe, < 40% predicted minute ventilation for at least 2 min). We evaluated for associations between clinical variables including minute ventilation prior to opioid administration and LMVe following the first PACU administration of opioid. Also assessed was a low respiratory rate (< 8 breaths per minute) as a proxy for LMVe. Of 107 patients, 38 (36%) had LMVe. Affected patients had greater intraoperative opioid dose, P = 0.05. PACU opioids were administered to 45 (42.1%) subjects, of which 27 (25.2%) had LMVe (P = 0.42) within 30 min following opioid. Pre-opioid minute ventilation < 70% of predicted normal value was associated with LMVe, P < 0.01, (sensitivity = 100%, specificity = 81%).Low respiratory rate was a poor predictor of LMVe (sensitivity = 11.8%). Other clinical variables (e.g., obstructive sleep apnea) were not found to be predictors of LMVe. Using RVM we identified that mild, clinically nondetectable, respiratory depression prior to opioid administration in the PACU was associated with the development of substantial subsequent respiratory depression during the PACU stay.

Isoflurane and postoperative respiratory depression following laparoscopic surgery: A retrospective propensity-matched analysis.

Episodes of respiratory depression during the immediate postoperative recovery period (Phase I post-anesthesia recovery) have been associated with respiratory complications during Phase II recovery. Using multivariable analyses in several surgical cohorts, we previously identified potential associations between patient and perioperative factors and increased risk for Phase I respiratory depression. The aim of this study is to use the propensity-matched analysis to specifically assess for a potential association between the use of isoflurane and episodes of Phase I respiratory depression after laparoscopic operations. The electronic medical records of 8567 patients who underwent laparoscopic operations between January 1, 2010 and July 31, 2014, lasting ≥90 minutes, were retrospectively analyzed. Propensity-matched patients anesthetized without isoflurane were identified for 3403 patients anesthetized with isoflurane. Compared to the use of desflurane, sevoflurane or propofol infusion, maintenance of anesthesia with isoflurane was associated with an increased likelihood of Phase I respiratory depression (OR 95% CI, 1.32, 1.15-1.50, p < 0.001) and longer Phase I recovery (126 vs. 110 minutes, p < 0.001). The use of isoflurane was associated with increased rates of postoperative respiratory depression and postoperative recovery when compared to sevoflurane, desflurane, or propofol infusion.

Perioperative outcomes of syndromic paraganglioma and pheochromocytoma resection in patients with von Hippel-Lindau disease, multiple endocrine neoplasia type 2, or neurofibromatosis type 1.

BACKGROUND: Pheochromocytoma and/or paraganglioma associated with neurofibromatosis type 1, multiple endocrine neoplasia type 2A, and von Hippel-Lindau disease have different catecholamine biochemical phenotypes. We examined perioperative outcomes of pheochromocytoma/paraganglioma resection in 3 syndromic forms. METHODS: Retrospective review of patients undergoing resection of syndromic pheochromocytoma/paraganglioma from 2000 through 2016. RESULTS: Eighty-one patients underwent pheochromocytoma/paraganglioma resection (multiple endocrine neoplasia type 2A, n = 36; neurofibromatosis type 1, n = 26; von Hippel-Lindau disease, n = 19). Tumor size differed across groups; patients with neurofibromatosis type 1 and von Hippel-Lindau disease had the largest tumors (P = .017). Larger tumor volumes correlated with higher urine 24-hour total metanephrine (r = 0.94, P < .001; r = 0.67, P = .033; and r = 0.89, P < .001 for multiple endocrine neoplasia type 2A, von Hippel-Lindau disease, and neurofibromatosis type 1, respectively). High adrenergic secretion (24-hour urine metanepinephrine) was found in neurofibromatosis type 1 (median, 861 µg/24 h), similar to that found in multiple endocrine neoplasia type 2A (median, 809 µg/24 h). The highest noradrenergic secretion (24-hour urine normetanephrine) occurred with von Hippel-Lindau disease (median, 4,598 µg/24 h), followed by neurofibromatosis type 1 and multiple endocrine neoplasia type 2A (median, 1,607 and 923 µg/24 h, respectively). The highest graded complications occurred among patients with neurofibromatosis type 1 (P = .036). However, when comparing postoperative outcomes across 3 groups in those who had laparoscopic resection, there was no significant difference (P = .955). CONCLUSION: Patients with neurofibromatosis type 1 had the most volatile intraoperative hemodynamic course and more severe postoperative complications. These complications are related to large tumors associated with abundant catecholamine secretion and the fact that a high proportion underwent open resection. Among only patients who underwent laparoscopic procedures, there were no differences in postoperative outcomes across syndromic groups.

Perioperative hemodynamics and outcomes of patients on metyrosine undergoing resection of pheochromocytoma or paraganglioma.

INTRODUCTION: To describe outcomes of patients with metyrosine (MET) pretreatment for abdominal surgical resection of pheochromocytoma or paraganglioma (PCC/PGL) compared with patients who had phenoxybenzamine (PBZ) pretreatment. METHODS: Retrospective review of perioperative outcomes for PCC/PGL patients treated with MET and propensity-matched comparison of MET and PBZ (MET + PBZ) with PBZ alone. RESULTS: MET preparation was given in 63 cases (26 laparoscopic and 37 open, of which 55 also received PBZ). All patients had wide perioperative hemodynamic oscillations. Patients with open procedures required more intravenous fluids and blood transfusions; 35% required postoperative vasopressor infusions for hypotension and 38% developed acute kidney injury. One laparoscopic procedure required postoperative vasopressor infusion, and 12% of patients developed acute kidney injury. Forty-five MET + PBZ patients were propensity-matched with PBZ-only patients. Intraoperatively, MET + PBZ patients had lower minimum systolic and diastolic blood pressures than PBZ-only patients (median systolic, 74 vs 80 mm Hg, P = 0.01; median diastolic, 42 vs 46 mm Hg, P = 0.005) and larger intraoperative blood pressure oscillations (median systolic range, 112 vs 93 mm Hg, P = 0.06; median diastolic range, 58 vs 51 mm Hg, P = 0.02). Postoperative vasopressor infusion use was similar between MET + PBZ and PBZ only (16% vs 11%, P = 0.76). Major outcomes were not different between regimens. CONCLUSION: Large hemodynamic oscillations were present in our PCC/PGL patients treated with MET + PBZ. These patients had a wider range of intraoperative blood pressure variations than PBZ-only patients. No differences in postoperative comorbid outcomes were found between MET + PBZ and PBZ-only groups.

Management in Neonatal Priapism: Case and Review.

Neonatal priapism is uncommon and its cause is usually unknown, but it can generate anxiety for the parents and the pediatric team. The treatment in most cases is conservative and no sequelae are described.

Perioperative risks of narcolepsy in patients undergoing general anesthesia: A case-control study.

STUDY OBJECTIVE: To compare the perioperative outcomes between patients with narcolepsy and matched controls undergoing anesthetic management. DESIGN: Retrospective 2:1 matched study design. SETTING: Large tertiary medical center. PATIENTS: Narcoleptic patients who underwent general anesthesia from January 1, 2011, through September 30, 2015, were matched with controls by age, sex, and type and year of surgery. MEASUREMENTS: Medical records were reviewed for episodes of respiratory depression during phase I recovery and for other meaningful perioperative outcomes. MAIN RESULTS: The perioperative courses of 76 narcoleptic patients and their controls were examined. Compared to controls, narcoleptic patients were more often prescribed central nervous system stimulants (73.7% vs 4.0%, P<0.001) and antidepressants (46.1% vs 27.6%, P=0.007) and more often had obstructive sleep apnea (40.8% vs 19.1%, P<0.001). The intraoperative course was similar. The number of episodes of respiratory depression was not different between patients and controls (5 [6.6%] vs 12 [7.9%], respectively; P=0.80). Narcoleptic patients had a higher frequency of emergency response team activations (5 of 76 [6.6%]; 95% CI, 2.2%-14.7%) compared to controls (2 of 152 [1.3%]; 95% CI, 0.2%-4.7%) (P=0.04). Hemodynamic instability was the indication for all emergency response team activations except 1, which was for a narcoleptic patient who had excessive postoperative sedation and respiratory depression. CONCLUSIONS: Narcoleptic patients had similar intraoperative courses as the matched controls, including phase I anesthetic recovery. However, they had a higher rate of emergency response team activations than the controls, which suggests that patients with narcolepsy may be at increased perioperative risk.

Congenital diaphragmatic hernia: outcomes of neonates treated at Mayo Clinic with and without extracorporeal membrane oxygenation.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a rare anomaly with high mortality and long-term comorbid conditions. AIMS: Our aim was to describe the presenting characteristics, treatment, and outcomes of consecutive patients with CDH treated at our institution. METHODS: We performed a retrospective cohort study and identified consecutive neonates treated for CDH from 2001 to 2015 at our institution. For all patients identified, we reviewed hospital and postdischarge data for neonatal, disease, and treatment characteristics. We determined hospital survival overall and also according to the presence of prenatal diagnosis, liver herniation into the chest (liver up), and the use of extracorporeal membrane oxygenation (ECMO) in addition to surgery. We evaluated postdischarge chronic conditions in patients with at least one year of follow-up. RESULTS: Thirty-eight neonates were admitted for treatment during the study period. In three who were in extremis, life support was withdrawn. The other 35 underwent surgical repair, of whom eight received ECMO. The overall survival was 79% (30/38). Survival for those who had surgical correction of CDH but did not need ECMO was 89% (24/27); it was 75% (6/8) for those who received ECMO and had surgery. Hospital survival was lower for liver-up vs liver-down CDH (61% [11/18] vs 95% [19/20]; odds ratio, 0.08; 95% CI, 0.01-0.77; P = 0.01). Among survivors, the median duration of hospitalization was 31 (interquartile range, 20-73) days. Major chronic pulmonary and gastrointestinal disorders, failure to thrive, and neurodevelopmental delays were the most noted comorbid conditions after discharge, and all were more prevalent in those who required ECMO. CONCLUSION: The overall survival of neonates with CDH was 79%. Intrathoracic liver herniation was associated with more frequent use of ECMO and greater mortality. A substantial number of survivors, especially those who required ECMO, experienced chronic conditions after discharge.

Multimodal Analgesic Therapy With Gabapentin and Its Association With Postoperative Respiratory Depression.

BACKGROUND: Gabapentinoids are widely used in perioperative multimodal analgesic regimens. The primary aim of this study was to determine whether gabapentin was associated with respiratory depression during phase-I postanesthesia recovery after major laparoscopic procedures. METHODS: We retrospectively reviewed the electronic health records of 8567 patients who underwent major laparoscopic procedures (lasting ≥90 minutes) from January 1, 2010, to July 31, 2014. We assessed potential associations among patient and perioperative variables and episodes of respiratory depression during phase-I recovery. Multivariable and propensity score-matched analyses were performed to assess potential associations between preoperative gabapentin use and postoperative respiratory depression. RESULTS: The incidence of respiratory depression was 153 (95% confidence interval [CI], 146-161) episodes per 1000 cases. Multivariable analysis showed that gabapentin was associated with respiratory depression (odds ratio [OR], 1.47 [95% CI, 1.22-1.76]; P < .001). These results were confirmed by propensity score-matched analysis among a subset of patients who did not have analgesia supplemented by intrathecal opioids (OR, 1.26 [95% CI, 1.02-1.58]; P = .04). Older patients and those who received more intraoperative opioids had increased risk of respiratory depression. Those who had an episode of respiratory depression had a longer phase-I recovery (P < .001) and an increased rate of admission to a higher level of care (P = .03). CONCLUSIONS: The use of gabapentin is associated with increased rates of respiratory depression among patients undergoing laparoscopic surgery. When gabapentinoids are included in multimodal analgesic regimens, intraoperative opioids must be reduced, and increased vigilance for respiratory depression may be warranted, especially in elderly patients.

Preoperative Levels of Catecholamines and Metanephrines and Intraoperative Hemodynamics of Patients Undergoing Pheochromocytoma and Paraganglioma Resection.

OBJECTIVE: To determine whether, despite pharmacologic adrenergic receptor blockade, higher preoperative levels of catecholamines and metanephrines (adrenergic activity) are associated with increased intraoperative complications. MATERIALS AND METHODS: Records of patients undergoing paraganglioma and pheochromocytoma (PGL-PCC) resection from January 1, 2000, to June 30, 2015, were reviewed for preoperative levels of adrenergic activity, intraoperative variability in blood pressure and heart rate (range), and postoperative outcomes (hypotension requiring treatment). Patients were categorized by maximum preoperative adrenergic activity by greater degree of abnormality, categorized as normal (≤100%) or 101%-200%, 201%-500%, 501%-1000%, and ≥1001% of upper limit of normal. RESULTS: In total, 258 patients underwent intrathoracic or intra-abdominal PGL-PCC resection, of whom 240 received pretreatment with nonselective α1,2-blockers and 7 received pretreatment with selective α1-blockers. Intraoperative hemodynamic variability was greater with higher preoperative levels of adrenergic activity (P <.001). However, substantial variability was observed even with adrenergic activity levels within the normal range: systolic blood pressure (median [interquartile range], 75 [63-83] mm Hg) and heart rate (34 [26-43] beats per minute). Among patients with preoperative levels of adrenergic activity ≤500% vs ≥501% of the upper limit of normal, higher levels were associated with greater likelihood of postoperative diagnosis of volume overload (8% vs 2%, P = .04) and greater requirement for vasopressor infusions for hypotension (5% vs 1%, P = .01). CONCLUSION: Substantial intraoperative hemodynamic instability was encountered in patients with PGL-PCC resection, regardless of preoperative hormonal activity level; therefore, universal preoperative adrenergic receptor blockade should be recommended. Postoperative hypotension was rare and more prevalent in those with higher preoperative hormonal activity.