John Snow and the First Second-Gas Effect.

In 1847, British anesthesia pioneer John Snow (1813-1858) observed that patients did not manifest cyanosis during induction with hypoxic mixtures of ether vapor in air. He hypothesized a molecular mechanism that would be understood over a century later as the second gas effect.

Effects of Intraoperative Fluid Management on Postoperative Outcomes: A Hospital Registry Study.

OBJECTIVE: Evaluate the dose-response relationship between intraoperative fluid administration and postoperative outcomes in a large cohort of surgical patients. BACKGROUND: Healthy humans may live in a state of fluid responsiveness without the need for fluid supplementation. Goal-directed protocols driven by such measures are limited in their ability to define the optimal fluid state during surgery. METHODS: This analysis of data on file included 92,094 adult patients undergoing noncardiac surgery with endotracheal intubation between 2007 and 2014 at an academic tertiary care hospital and two affiliated community hospitals. The primary exposure variable was total intraoperative volume of crystalloid and colloid administered. The primary outcome was 30-day survival. Secondary outcomes were respiratory complications within three postoperative days (pulmonary edema, reintubation, pneumonia, or respiratory failure) and acute kidney injury. Exploratory outcomes were postoperative length of stay and total cost of care. Our models were adjusted for patient-, procedure-, and anesthesia-related factors. RESULTS: A U-shaped association was observed between the volume of fluid administered intraoperatively and 30-day mortality, costs, and postoperative length of stay. Liberal fluid volumes (highest quintile of fluid administration practice) were significantly associated with respiratory complications whereas both liberal and restrictive (lowest quintile) volumes were significantly associated with acute kidney injury. Moderately restrictive volumes (second quintile) were consistently associated with optimal postoperative outcomes and were characterized by volumes approximately 40% less than traditional textbook estimates: infusion rates of approximately 6-7 mL/kg/hr or 1 L of fluid for a 3-hour case. CONCLUSIONS: Intraoperative fluid dosing at the liberal and restrictive margins of observed practice is associated with increased morbidity, mortality, cost, and length of stay.

Dose-Dependent Protective Effect of Inhalational Anesthetics Against Postoperative Respiratory Complications: A Prospective Analysis of Data on File From Three Hospitals in New England.

OBJECTIVES: Inhalational anesthetics are bronchodilators with immunomodulatory effects. We sought to determine the effect of inhalational anesthetic dose on risk of severe postoperative respiratory complications. DESIGN: Prospective analysis of data on file in surgical cases between January 2007 and December 2015. SETTING: Massachusetts General Hospital (tertiary referral center) and two affiliated community hospitals. PATIENTS: A total of 124,497 adult patients (105,267 in the study cohort and 19,230 in the validation cohort) undergoing noncardiac surgical procedures and requiring general anesthesia with endotracheal intubation. INTERVENTIONS: Median effective dose equivalent of inhalational anesthetics during surgery (derived from mean end-tidal inhalational anesthetic concentrations). MEASUREMENTS AND MAIN RESULTS: Postoperative respiratory complications occurred in 6,979 of 124,497 cases (5.61%). High inhalational anesthetic dose of 1.20 (1.13-1.30) (median [interquartile range])-fold median effective dose equivalent versus 0.57 (0.45-0.64)-fold median effective dose equivalent was associated with lower odds of postoperative respiratory complications (odds ratio, 0.59; 95% CI, 0.53-0.65; p < 0.001). Additionally, high inhalational anesthetic dose was associated with lower 30-day mortality and lower cost. Inhalational anesthetic dose increase and reduced risk of postoperative respiratory complications remained significant in sensitivity analyses stratified by preoperative and intraoperative risk factors. CONCLUSIONS: Intraoperative use of higher inhalational anesthetic doses is strongly associated with lower odds of postoperative respiratory complications, lower 30-day mortality, and lower cost of hospital care. The authors speculate based on these data that sedation with inhalational anesthetics outside of the operating room may likewise have protective effects that decrease the risk of respiratory complications in vulnerable patients.

Continuous Positive Airway Pressure Mitigates Opioid-induced Worsening of Sleep-disordered Breathing Early after Bariatric Surgery.

BACKGROUND: Bariatric surgery patients are vulnerable to sleep-disordered breathing (SDB) early after recovery from surgery and anesthesia. The authors hypothesized that continuous positive airway pressure (CPAP) improves postoperative oxygenation and SDB and mitigates opioid-induced respiratory depression. METHODS: In a randomized crossover trial, patients after bariatric surgery received 30% oxygen in the postanesthesia care unit (PACU) under two conditions: atmospheric pressure and CPAP (8 to 10 cm H2O). During 1 h of each treatment, breathing across cortical arousal states was analyzed using polysomnography and spirometry. Arousal state and respiratory events were scored in accordance with American Academy of Sleep Medicine guidelines. Data on opioid boluses in the PACU were collected. The primary and secondary outcomes were the apnea hypopnea index (AHI) and apnea after self-administration of opioids in the PACU. Linear mixed model analysis was used to compare physiologic measures of breathing. RESULTS: Sixty-four percent of the 33 patients with complete postoperative polysomnography data demonstrated SDB (AHI greater than 5/h) early after recovery from anesthesia. CPAP treatment decreased AHI (8 ± 2/h vs. 25 ± 5/h, P < 0.001), decreased oxygen desaturations (5 ± 10/h vs. 16 ± 20/h, P < 0.001), and increased the mean oxygen saturation by 3% (P = 0.003). CPAP significantly decreased the respiratory-depressant effects observed during wakefulness-sleep transitions without affecting hemodynamics. The interaction effects between CPAP treatment and opioid dose for the dependent variables AHI (P < 0.001), inspiratory flow (P = 0.002), and minute ventilation (P = 0.015) were significant. CONCLUSIONS: This pharmacophysiologic interaction trial shows that supervised CPAP treatment early after surgery improves SDB and ameliorates the respiratory-depressant effects of opioids without undue hemodynamic effects.

Effects of obstructive sleep apnoea risk on postoperative respiratory complications: protocol for a hospital-based registry study.

INTRODUCTION: Obstructive sleep apnoea (OSA), the most common type of sleep-disordered breathing, is associated with significant immediate and long-term morbidity, including fragmented sleep and impaired daytime functioning, as well as more severe consequences, such as hypertension, impaired cognitive function and reduced quality of life. Perioperatively, OSA occurs frequently as a consequence of pre-existing vulnerability, surgery and drug effects. The impact of OSA on postoperative respiratory complications (PRCs) needs to be better characterised. As OSA is associated with significant comorbidities, such as obesity, pulmonary hypertension, myocardial infarction and stroke, it is unclear whether OSA or its comorbidities are the mechanism of PRCs. This project aims to (1) develop a novel prediction score identifying surgical patients at high risk of OSA, (2) evaluate the association of OSA risk on PRCs and (3) evaluate if pharmacological agents used during surgery modify this association. METHODS: Retrospective cohort study using hospital-based electronic patient data and perioperative data on medications administered and vital signs. We will use data from Partners Healthcare clinical databases, Boston, Massachusetts. First, a prediction model for OSA will be developed using OSA diagnostic codes and polysomnography procedural codes as the reference standard, and will be validated by medical record review. Results of the prediction model will be used to classify patients in the database as high, medium or low risk of OSA, and we will investigate the effect of OSA on risk of PRCs. Finally, we will test whether the effect of OSA on PRCs is modified by the use of intraoperative pharmacological agents known to increase upper airway instability, including neuromuscular blockade, neostigmine, opioids, anaesthetics and sedatives. ETHICS AND DISSEMINATION: The Partners Human Research Committee approved this study (protocol number: 2014P000218). Study results will be made available in the form of manuscripts for publication and presentations at national and international meetings.