Guidance for the use and reporting of anaesthetic agents in BJP manuscripts involving work with animals.

Scientists who plan to publish in the British Journal of Pharmacology (BJP) should read this article before undertaking studies utilising anaesthetics in mammalian animals. This editorial identifies certain gaps in the reporting of details on the use of anaesthetics in animal research studies published in the BJP. The editorial also provides guidance, based upon current best practices, for performing in vivo experiments that require anaesthesia. In addition, mechanisms of action and physiological impact of specific anaesthetic agents are discussed. Our goal is to identify best practices and to provide guidance on the information required for manuscripts submitted to the BJP that involve the use of anaesthetic agents in studies with experimental animals.

The Association of Preoperative Smoking With Postoperative Outcomes in Patients Undergoing Total Hip Arthroplasty.

BACKGROUND: Preoperative smoking is an easily modifiable risk factor and has associations with increased postoperative morbidity and mortality. It is important to clarify these risks for specific procedures to provide improved and evidence-based quality of care. The purpose of the present study aims to identify the associations between preoperative smoking and 30-day postoperative outcomes in patients undergoing total hip arthroplasty. METHODS: We used R statistics to conduct a multivariable logistic regression analysis followed by a propensity score matching analysis to explore the association between preoperative smoking and postoperative outcomes. RESULTS: A final cohort of 67,897 patients who underwent total hip arthroplasty was selected for analysis. After adjusting for potential confounders, the odds of postoperative pulmonary complications (odds ratio [OR], 1.352; 95% confidence interval [95% CI], 1.075-1.700; P = .01), infectious complications (OR, 1.310; 95% CI, 1.094-1.567; P = .003), and extended hospital stay (OR, 1.17; 95% CI, 1.099-1.251; P < .001) were all significantly higher in the smoking population. After propensity matching these cohorts, both infectious complications (P = .017) and extended hospital stays (P = .001) were significantly higher in smoking patients. CONCLUSIONS: After controlling for potential confounding variables, our multivariable regression analysis revealed a significant increase in pulmonary and infectious complications as well as significantly longer hospital stays in our smoking population. When using a propensity score matching analysis, an increase in infectious complications as well as extended hospital stay was observed. Given the concerning prevalence of smoking in the United States, our data provide updated information toward a growing mass of literature supporting smoking cessation before surgical operations.

The Performance of an Artificial Neural Network Model in Predicting the Early Distribution Kinetics of Propofol in Morbidly Obese and Lean Subjects.

BACKGROUND: Induction of anesthesia is a phase characterized by rapid changes in both drug concentration and drug effect. Conventional mammillary compartmental models are limited in their ability to accurately describe the early drug distribution kinetics. Recirculatory models have been used to account for intravascular mixing after drug administration. However, these models themselves may be prone to misspecification. Artificial neural networks offer an advantage in that they are flexible and not limited to a specific structure and, therefore, may be superior in modeling complex nonlinear systems. They have been used successfully in the past to model steady-state or near steady-state kinetics, but never have they been used to model induction-phase kinetics using a high-resolution pharmacokinetic dataset. This study is the first to use an artificial neural network to model early- and late-phase kinetics of a drug. METHODS: Twenty morbidly obese and 10 lean subjects were each administered propofol for induction of anesthesia at a rate of 100 mg/kg/h based on lean body weight and total body weight for obese and lean subjects, respectively. High-resolution plasma samples were collected during the induction phase of anesthesia, with the last sample taken at 16 hours after propofol administration for a total of 47 samples per subject. Traditional mammillary compartment models, recirculatory models, and a gated recurrent unit neural network were constructed to model the propofol pharmacokinetics. Model performance was compared. RESULTS: A 4-compartment model, a recirculatory model, and a gated recurrent unit neural network were assessed. The final recirculatory model (mean prediction error: 0.348; mean square error: 23.92) and gated recurrent unit neural network that incorporated ensemble learning (mean prediction error: 0.161; mean square error: 20.83) had similar performance. Each of these models overpredicted propofol concentrations during the induction and elimination phases. Both models had superior performance compared to the 4-compartment model (mean prediction error: 0.108; mean square error: 31.61), which suffered from overprediction bias during the first 5 minutes followed by under-prediction bias after 5 minutes. CONCLUSIONS: A recirculatory model and gated recurrent unit artificial neural network that incorporated ensemble learning both had similar performance and were both superior to a compartmental model in describing our high-resolution pharmacokinetic data of propofol. The potential of neural networks in pharmacokinetic modeling is encouraging but may be limited by the amount of training data available for these models.

An integrated microcatheter-based dual-analyte sensor system for simultaneous, real-time measurement of propofol and fentanyl.

According to the American Society of Anesthesiologists Closed Claims Database, one of three drug-related errors is the result administrating an incorrect dose. Directly measuring drug concentration removes the uncertainty in the dose-concentration relationship and addresses inter- and intra-subject variabilities that affect the pharmacokinetics of anesthetics. Here we describe a dual-analyte microcatheter-based electrochemical sensor capable of simultaneous real-time continuous monitoring of fentanyl (FTN) and propofol (PPF) drugs simultaneously in the operating rooms. Such a dual PPF/FTN catheter sensor relies on embedding two different modified carbon paste (CP)-packed working electrodes along with Ag/AgCl microwire reference electrodes within a mm-wide Teflon tube, and uses a square wave voltammetric (SWV) technique. The composition of each working electrode was judiciously tailored to cover the concentration range of interest for each analyte. A polyvinyl chloride (PVC) organic polymer coating on the surface of CP electrode enabled selective and sensitive PPF measurements in µM range. The detection of nM FTN levels was achieved through a multilayered nanostructure-based surface modification protocol, including a CNT-incorporated CP transducer modified by a hybrid of electrodeposited Au nanoparticles and electrochemically reduced graphene oxide (erGO) and a PVC outer membrane. The long-term monitoring capability of the dual sensor was demonstrated in a protein-rich artificial plasma medium. The promising antibiofouling behavior of the catheter-based multiplexed sensor was also illustrated in whole blood samples. The new integrated dual-sensor microcatheter platform holds considerable promise towards real-time, in-vivo detection of the anesthetic drugs, propofol and fentanyl, during surgical procedures towards significantly improved safe delivery of anesthetic drugs.

The association of body mass index with same-day hospital admission, postoperative complications, and 30-day readmission following day-case eligible joint arthroscopy: A national registry analysis.

STUDY OBJECTIVE: We examined the association of body mass index (BMI) with hospital admission, same-day complications, and 30-day hospital readmission following day-case eligible joint arthroscopy. DESIGN: Retrospective cohort study. SETTING: Multi-institutional. PATIENTS: Adult patients undergoing arthroscopy of the knee, hip or shoulder in the outpatient setting. INTERVENTION: None. MEASUREMENTS: Using the American College of Surgeons National Surgical Quality Improvement Program dataset from 2012 to 2016, we examined seven BMI ranges: normal BMI (≥20 kg/m2 and <25 kg/m2), underweight (<20 kg/m2), overweight (≥25 kg/m2 and <30 kg/m2), Class 1 and 2 obese (≥30 kg/m2 and <40 kg/m2, reference variable), and severe obesity, which we divided into the following BMI ranges: ≥40 kg/m2 and <50 kg/m2, ≥50 kg/m2 and <60 kg/m2, and ≥60 kg/m2. The primary outcome was hospital admission. Secondary outcomes included same-day postoperative complications and 30-day hospital readmission. We performed multivariable logistic regression and reported odds ratios (OR) and their associated 95% confidence interval (CI) and considered a p-value of <0.05 as statistically significant. MAIN RESULTS: There were a total of 99,410 patients included in the final analysis, in which there was a 2.6% rate of hospital admission. When compared to class 3 obesity, only those with BMI ≥50 kg/m2(OR 1.55, 95% CI 1.18-2.01, p = 0.005) had increased odds of hospital admission. There were no differences in 30-day hospital readmission or same-day postoperative complications. CONCLUSION: We found that only patients with BMI ≥50 kg/m2 had increased odds for same-day hospital admission even when patient's comorbid conditions are optimized, suggesting that a BMI ≥50 kg/m2 may be used as a sole factor for patient selection in patients undergoing joint arthroscopy. For patients with BMI <50 kg/m2, we recommend that BMI alone should not be solely used to exclude patients from having joint arthroscopies performed in an outpatient setting, especially since this patient group makes up a significant proportion of joint arthroscopy.

Association of Primary Anesthesia Type with Postoperative Adverse Events After Transcarotid Artery Revascularization.

OBJECTIVES: The literature remains sparse regarding the influence of primary anesthesia type (monitored anesthesia care [MAC] v general anesthesia) on 30-day adverse events after transcarotid artery revascularization (TCAR). The objective of this study was to report the association of primary anesthesia type with 30-day adverse events after TCAR. DESIGN: Retrospective cohort analysis of the American College of Surgeons National Surgical Quality Improvement Program Registry from 2012-2016. SETTING: Multi-institutional. PARTICIPANTS: The final analysis included 625 patients who underwent TCAR. INTERVENTIONS: The primary exposure was anesthesia type, categorized as MAC (defined as regional anesthesia, local anesthesia, or MAC) or general anesthesia. The primary endpoint was 30-day mortality. Secondary 30-day endpoints included pulmonary, renal, and cardiac complications; sepsis; deep venous thrombosis; stroke; blood transfusion; embolism/thrombosis of ipsilateral carotid vessel; and redo surgery. MEASUREMENTS AND MAIN RESULTS: The prevalence of MAC was 73.4%. A 93% decrease was observed in the odds of 30-day mortality (p = 0.003) in patients who received MAC. Mean (standard deviation) hospital stay (2.99 [5.92] d v 4.30 [9.15] d; p = 0.037) and case duration (88.45 [39.48] min v 105.85 [63.77] min; p < 0.001) were shorter among patients who received MAC. The odds of pulmonary complications (odds ratio 0.19, 95% confidence interval 0.05-0.65; p = 0.009) were significantly lower in the MAC group. No other differences in secondary endpoints were found between the anesthesia type cohorts. CONCLUSIONS: The majority of studies on this topic pertain to carotid endarterectomy patients, and this retrospective analysis sheds light on outcomes after TCAR. Overall, the authors urge additional risk stratification and preprocedural optimization to carefully select patients who may undergo MAC.

The association of preoperative delirium with postoperative outcomes following hip surgery in the elderly.

STUDY OBJECTIVE: To determine the association of preoperative delirium with postoperative outcomes following hip surgery in the elderly. DESIGN: Retrospective cohort study. SETTING: Postoperative recovery. PATIENTS: 8466 patients all of whom were 65 years of age or older undergoing surgical repair of a femoral fracture. Of the total population studied, 1075 had preoperative delirium. Of those with preoperative delirium, 746 were ASA class 3 or below and 327 were ASA class 4 or above. Of the 7391 patients without preoperative delirium, 5773 were ASA class 3 or below and 1605 were ASA class 4 or above. The remainder in each group was of unknown ASA class. INTERVENTIONS: We used multivariable logistic regression to explore the association of preoperative delirium with 30-day postoperative outcomes. The odds ratio (OR) with associated 95% confidence interval (CI) was reported for each covariate. MEASUREMENTS: Data was collected regarding the incidence of postoperative outcomes including: delirium, pulmonary complications, extended hospital stay, infection, renal complications, vascular complications, cardiac complications, transfusion necessity, readmission, and mortality. MAIN RESULTS: After adjusting for potential confounders, the odds of postoperative delirium (OR 9.38, 95% CI 7.94-11.14), pulmonary complications (OR 1.83, 95% CI 1.4-2.36), extended hospital stay (OR 1.47, 95% CI 1.26-1.72), readmission (OR 1.27, 95% CI 1.01-1.59) and mortality (OR 1.92, 95% CI 1.54-2.39) were all significantly higher in patients with preoperative delirium compared to those without. CONCLUSIONS: After controlling for potential confounding variables, we showed that preoperative delirium was associated with postoperative delirium, pulmonary complications, extended hospital stay, hospital readmission, and mortality. Given the lack of studies on preoperative delirium and its postoperative outcomes, our data provides a strong starting point for further investigations as well as the development and implementation of targeted risk-reduction programs.

Pharmacokinetics of Cefazolin and Vancomycin in Infants Undergoing Open-Heart Surgery With Cardiopulmonary Bypass.

BACKGROUND: Gram-positive bacteria account for nearly three-quarters of all surgical site infections. Antibiotic prophylaxis against these bacteria with cephalosporins or, in select circumstances, with vancomycin is considered standard of care for prevention of surgical site infections. There is little evidence to describe the optimal dosing regimen for surgical site infection prophylaxis in infants undergoing cardiac surgery, and a great deal of institutional variability exists in dosing prophylactic antibiotics. We designed this study to describe an optimal dose regimen for cephalosporin and vancomycin based on pharmacokinetic evidence for infant open-heart surgery on cardiopulmonary bypass. METHODS: Two separate cohorts of infants undergoing cardiac surgery with cardiopulmonary bypass were evaluated. Plasma concentrations of vancomycin (cohort 1, N = 10) and cefazolin (cohort 2, N = 10) were measured, and mixed-effects pharmacokinetic models were constructed for each drug. Simulations of various dosing regimens were performed to describe an appropriate dosing regimen necessary to maintain antibiotic concentrations above the susceptibility cutoff for staphylococci. RESULTS: Both cefazolin and vancomycin plasma concentration versus time profiles were characterized by a 2-compartment model. Subject weight was a significant covariate for V1 for vancomycin. Subject age was a significant covariate for V1 for cefazolin. Cardiopulmonary bypass did not influence concentration versus time profiles. Simulations demonstrated that a 1-hour vancomycin infusion (15 mg·kg), repeated every 12 hours and a 10-minute infusion of cefazolin (30 mg·kg), repeated every 4 hours maintained plasma concentrations above 4 µg·mL and 16 µg·mL, for vancomycin and cefazolin, respectively. Both concentrations are above the minimum inhibitory concentration 90 for most susceptible staphylococci. CONCLUSIONS: Prophylactic treatment of vancomycin 15 mg·kg infused >1 hour with 12-hour redosing and cefazolin 30 mg·kg infused >10 minutes with 4-hour redosing will maintain serum levels of each antibiotic above the susceptibility cut-offs for susceptible staphylococci in infants undergoing cardiac surgery. Cefazolin levels may be adequate for some, but not all, Gram-negative bacteria. The effect of cardiopulmonary bypass on pharmacokinetics is negligible.

Tracheal Stenosis Because of Wegener Granulomatosis Misdiagnosed as Asthma.

We describe a patient with Wegener granulomatosis whose complaint of wheezing was incorrectly attributed to asthma. Anesthesiologists must recognize that tracheal stenosis is extremely common in Wegener granulomatosis and can mimic other causes of wheezing.

The impact of blood pressure cuff location on the accuracy of noninvasive blood pressure measurements in obese patients: an observational study.

PURPOSE: Obesity presents many challenges to the anesthesiologist, including poorly fitting blood pressure (BP) cuffs due to the conical shape of the upper arm. The aim of this study was to determine the accuracy of noninvasive BP readings, obtained from a noninvasive BP cuff using various cuff locations and wrapping techniques, compared with invasive intra-arterial BP readings. METHODS: Thirty American Society of Anesthesiologists physical status I-III obese (body mass index > 30 kg·m(-2)) individuals undergoing non-cardiac surgery were enrolled in this observational study. Serial oscillometric noninvasive BP (NIBP) measurements were taken in the patients' forearm and upper arm with two different wrapping formations (one following the contour of the upper arm, the other keeping cuff edges parallel). These NIBP measurements were compared with invasive arterial blood pressure (ABP) measurements taken from the ipsilateral radial artery. The precision and bias of the NIBP and ABP measurements were determined using Bland-Altman analysis. Analysis of variance and Welch's t test were used to determine between-group differences in bias. RESULTS: There was poor agreement between the ABP measurements and all types of NIBP measurements. Each of our study participants had a least one NIBP parameter (mean arterial pressure, systolic BP, or diastolic BP) that was > 10 mmHg different than the corresponding ABP parameter. Upper arm BP measurements showed a statistically insignificant trend toward underestimating ABP. For all cuff positions and wrapping techniques, systolic BP offered the best agreement between NIBP and ABP measurements. CONCLUSIONS: All the forms of NIBP cuff orientation studied had unacceptable precision and bias compared with invasive ABP measurements. When patient and/or surgical conditions necessitate accurate BP monitoring, direct arterial measurement should be considered over NIBP measurements in obese patients.

Medical devices for the anesthetist: current perspectives.

Anesthesiologists are unique among most physicians in that they routinely use technology and medical devices to carry out their daily activities. Recently, there have been significant advances in medical technology. These advances have increased the number and utility of medical devices available to the anesthesiologist. There is little doubt that these new tools have improved the practice of anesthesia. Monitoring has become more comprehensive and less invasive, airway management has become easier, and placement of central venous catheters and regional nerve blockade has become faster and safer. This review focuses on key medical devices such as cardiovascular monitors, airway equipment, neuromonitoring tools, ultrasound, and target controlled drug delivery software and hardware. This review demonstrates how advances in these areas have improved the safety and efficacy of anesthesia and facilitate its administration. When applicable, indications and contraindications to the use of these novel devices will be explored as well as the controversies surrounding their use.

Anesthetic Pharmacology and the Morbidly Obese Patient.

Anesthesiologists are increasingly being faced with treating obese patients. Physiologic and anthropometric associated with obesity-most notably increases in cardiac output, changes in tissue perfusion and increases in total body weight (TBW), lean body weight (LBW), and fat mass affect the pharmacokinetics (PK) of anesthetic agents. In addition, redundancy of airway tissue, obstructive and central sleep apnea and CO2 retention affect the pharmacodynamics (PD) of anesthetics and narrow the therapeutic window of numerous anesthetic drugs. Safe and effective pharmacologic management of the obese patient requires a thorough understanding of how obesity affects the PK and PD of anesthetics.

Perioperative management of the morbidly obese adolescent with heart failure undergoing bariatric surgery.

The incidence and prevalence of adolescent obesity and adolescent heart failure are increasing, and anesthesiologists increasingly will encounter patients with both conditions. A greater understanding of the physiologic challenges of adolescent heart failure as they relate to the perioperative stressors of anesthesia and bariatric surgery is necessary to successfully manage the perioperative risks faced by this growing subpopulation. Here, we present a representative case of a morbidly obese adolescent with heart failure who underwent a laparoscopic bariatric operation and review the limited available literature on perioperative management in this age group. Specifically, we review evidence and offer recommendations related to preoperative evaluation, venous thromboembolism prophylaxis, positioning, induction, airway management, monitoring, anesthetic maintenance, ventilator management, and adverse effects of the pneumoperitoneum, rhabdomyolysis, and postoperative care.