Perioperative Outcomes After Preoperative Epidural Analgesia in Patients with Hip Fracture Undergoing Surgical Repair: A Systematic Review.

OBJECTIVE: To examine the effectiveness and safety of epidural analgesia in the presurgical period in patients with hip fracture undergoing surgical repair. DESIGN: Systematic review. METHODS: The study protocol was registered with the PROSPERO systematic reviews registry with the (identifier CRD42019140396). Electronic databases were searched for randomized controlled trials comparing preoperative epidural analgesia with other forms of pain management in patients with a hip fracture. The primary outcomes included perioperative cardiac events and death. Pain, noncardiac complications, and adverse effects were also examined as secondary outcomes. The heterogeneity of the included studies was assessed with the I2 statistic, and a random-effects meta-analysis was conducted once sufficient homogeneity was demonstrated. RESULTS: Four studies, which included a total of 221 patients, met the inclusion criteria. Preoperative epidural analgesia resulted in fewer cardiac events, which was a reported outcome in two included studies (relative risk 0.30; 95% confidence interval 0.14-0.63; I2=0%). Preoperative epidural analgesia was also associated with a decreased perioperative mortality rate in a meta-analysis of two studies (relative risk 0.13; 95% confidence interval 0.02-0.98; I2 = 0%). Pain was not pooled because of variability in assessment methods, but preoperative epidural analgesia was associated with reduced pain in all four studies. CONCLUSIONS: Preoperative epidural analgesia for hip fracture may reduce perioperative cardiac events and deaths, but the number of included studies in this systematic review was low. More research should be done to determine the benefit of early epidural analgesia for patients with hip fracture.

The Effect of Low-Dose Intraoperative Ketamine on Closed-Loop-Controlled General Anesthesia: A Randomized Controlled Equivalence Trial.

BACKGROUND: Closed-loop control of propofol-remifentanil anesthesia using the processed electroencephalography depth-of-hypnosis index provided by the NeuroSENSE monitor (WAVCNS) has been previously described. The purpose of this placebo-controlled study was to evaluate the performance (percentage time within ±10 units of the setpoint during the maintenance of anesthesia) of a closed-loop propofol-remifentanil controller during induction and maintenance of anesthesia in the presence of a low dose of ketamine. METHODS: Following ethical approval and informed consent, American Society of Anesthesiologist (ASA) physical status I-II patients aged 19-54 years, scheduled for elective orthopedic surgery requiring general anesthesia for >60 minutes duration, were enrolled in a double-blind randomized, placebo-controlled, 2-group equivalence trial. Immediately before induction of anesthesia, participants in the ketamine group received a 0.25 mg·kg-1 bolus of intravenous ketamine over 60 seconds followed by a continuous 5 µg·kg-1·min-1 infusion for up to 45 minutes. Participants in the control group received an equivalent volume of normal saline. After the initial study drug bolus, closed-loop induction of anesthesia was initiated; propofol and remifentanil remained under closed-loop control until the anesthetic was tapered and turned off at the anesthesiologist's discretion. An equivalence range of ±8.99% was assumed for comparing controller performance. RESULTS: Sixty patients participated: 41 males, 54 ASA physical status I, with a median (interquartile range [IQR]) age of 29 [23, 38] years and weight of 82 [71, 93] kg. Complete data were available from 29 cases in the ketamine group and 27 in the control group. Percentage time within ±10 units of the WAVCNS setpoint was median [IQR] 86.6% [79.7, 90.2] in the ketamine group and 86.4% [76.5, 89.8] in the control group (median difference, 1.0%; 95% confidence interval [CI] -3.6 to 5.0). Mean propofol dose during maintenance of anesthesia for the ketamine group was higher than for the control group (median difference, 24.9 µg·kg-1·min-1; 95% CI, 6.5-43.1; P = .005). CONCLUSIONS: Because the 95% CI of the difference in controller performance lies entirely within the a priori equivalence range, we infer that this analgesic dose of ketamine did not alter controller performance. Further study is required to confirm the finding that mean propofol dosing was higher in the ketamine group, and to investigate the implication that this dose of ketamine may have affected the WAVCNS.

Effect of ketamine on the NeuroSENSE WAVCNS during propofol anesthesia; a randomized feasibility trial.

Dose-dependent effects of ketamine on processed electroencephalographic depth-of-hypnosis indices have been reported. Limited data are available for the NeuroSENSE WAVCNS index. Our aim was to establish the feasibility of closed-loop propofol-remifentanil anesthesia guided by the WAVCNS index in the presence of an analgesic dose of ketamine. Thirty ASA I-II adults, 18-54 years, requiring general anesthesia for anterior cruciate ligament surgery were randomized to receive: full-dose [ketamine, 0.5 mg kg-1 initial bolus, 10 mcg kg-1 min-1 infusion] (recommended dose for postoperative pain management); half-dose [ketamine, 0.25 mg kg-1 bolus, 5 mcg kg-1 min-1 infusion]; or control [no ketamine]. After the ketamine bolus, patients received 1.0 mcg kg-1 remifentanil over 30 s, then 1.5 mg kg-1 propofol over 30 s, followed by manually-adjusted propofol-remifentanil anesthesia. The WAVCNS was > 60 for 7/9 patients in the full-dose group at 7 min after starting the propofol infusion. This was inconsistent with clinical observations of depth-of-hypnosis and significantly higher than control (median difference [MD] 17.0, 95% confidence interval [CI] 11.4-26.8). WAVCNS was median [interquartile range] 49.3 [42.2-62.6] in the half-dose group, and not different to control (MD 5.1, 95% CI - 4.9 to 17.9). During maintenance of anesthesia, the WAVCNS was higher in the full-dose group compared to control (MD 14.7, 95% CI 10.2-19.2) and in the half-dose group compared to control (MD 11.4, 95% CI 4.7-20.4). The full-dose of ketamine recommended for postoperative pain management had a significant effect on the WAVCNS. This effect should be considered when using the WAVCNS to guide propofol-remifentanil dosing.Trial Registration ClinicalTrails.gov No. NCT02908945.

The effect of ketamine on depth of hypnosis indices during total intravenous anesthesia-a comparative study using a novel electroencephalography case replay system.

Ketamine may affect the reliability of electroencephalographic (EEG) depth-of-hypnosis indices as it affects power in high-frequency EEG components. The purpose of this study was to compare the effects of ketamine on three commonly-used depth-of-hypnosis indices by extending our EEG simulator to allow replay of previously-recorded EEG. Secondary analysis of previously-collected data from a randomized controlled trial of intravenous anesthesia with ketamine: Group 0.5 [ketamine, 0.5 mg kg-1 bolus followed by a 10 mcg kg-1 min-1 infusion], Group 0.25 [ketamine, 0.25 mg kg-1 bolus, 5 mcg kg-1 min-1 infusion], and Control [no ketamine]. EEG data were replayed to three monitors: NeuroSENSE (WAV), Bispectral Index (BIS), and Entropy (SE). Differences in depth-of-hypnosis indices during the initial 15 min after induction of anesthesia were compared between monitors, and between groups. Monitor agreement was evaluated using Bland-Altman analysis. Available data included 45.6 h of EEG recordings from 27 cases. Ketamine was associated with higher depth-of-hypnosis index values measured at 10 min (BIS, χ2 = 8.01, p = 0.018; SE, χ2 = 11.44, p = 0.003; WAV, χ2 = 9.19, p = 0.010), and a higher proportion of index values > 60 for both ketamine groups compared to the control group. Significant differences between monitors were not observed, except between BIS and SE in the control group. Ketamine did not change agreement between monitors. The ketamine-induced increase in depth-of-hypnosis indices was observed consistently across the three EEG monitoring algorithms evaluated. The observed increase was likely caused by a power increase in the beta and gamma bands. However, there were no lasting differences in depth-of-hypnosis reported between the three compared indices.

Slated versus actual operating room entry time in a British Columbia health authority.

PURPOSE: To determine how frequently the published operating room (OR) schedule of case start times correlated with the actual OR entry time for elective cases in the Fraser Health Authority (FHA) in British Columbia, Canada. Society guidelines recommend periods of fasting of two hours prior to the induction of general anesthesia, but patients frequently end up fasting much longer. This review aimed to determine when patients arrive in the OR-either earlier than their scheduled time or later. The premise of some is that patients often arrive earlier, and advising short fasting times on the basis of the OR slate time is unreliable. I wished to determine whether this fear is justified. METHODS: The computerized OR management database was queried for slated time of entry and actual time of entry for elective surgical cases in 11 hospitals in the FHA. The difference in slated vs actual entry time of patients (in 30 min blocks) was reviewed to examine the proportion of patients entering the OR earlier than 90 min from their slated time. Additionally, anesthesiologists from the Royal Columbian/Eagle Ridge Hospitals were surveyed for their recall of case delays that were related to inappropriate consumption of fluids. RESULTS: One hundred and twenty-three thousand eight hundred and sixty-five cases from 11 hospitals over a 32-month period were analyzed. A very small proportion of cases (753 of 123,865 cases, 0.6%) entered the OR earlier than 90 min from their slated time. Relatively few cases were actually cancelled because of inappropriate fluid consumption in the recall of anesthesiologists in two institutions. CONCLUSION: In the FHA, the OR schedule is a reliable guide to providing instructions on timing of preoperative fluid consumption in appropriately selected elective surgical patients. Quality of care and patient satisfaction will safely be enhanced by limiting the period of fasting for elective surgical patients.

RéSUMé: OBJECTIF: Nous avions pour objectif de déterminer à quelle fréquence les heures de début de cas planifiées et publiées dans le programme opératoire correspondaient aux heures réelles d'entrée en salle d'opération (SOP) pour les cas non urgents réalisés dans le réseau de l'autorité sanitaire Fraser (FHA) en Colombie-Britannique, au Canada. Les directives de la Société préconisent des périodes de jeûne de deux heures avant l'induction de l'anesthésie générale, mais les patients sont souvent à jeun pour bien plus longtemps. Ce compte-rendu avait pour objectif de déterminer le moment où les patients arrivent effectivement en SOP ­ soit plus tôt que l'heure planifiée, ou plus tard. La prémisse de certains est que les patients arrivent souvent plus tôt, et il n'est donc pas fiable de recommander des temps de jeûne plus courts en fonction de l'heure planifiée en SOP. Je souhaitais déterminer si cette crainte était fondée. MéTHODE: La base de données informatisée de gestion de la SOP a été consultée afin d'en extraire l'heure prévue et l'heure réelle d'entrée en SOP des cas chirurgicaux non urgents dans 11 hôpitaux du réseau FHA. La différence entre l'heure d'entrée prévue vs réelle des patients (en blocs de 30 min) a été passée en revue afin d'examiner la proportion de patients entrant en SOP plus de 90 min plus tôt que l'heure prévue. En outre, les anesthésiologistes des hôpitaux Royal Columbian/Eagle Ridge ont été sondés concernant leurs souvenirs de retards de cas liés à une consommation inappropriée de liquides. RéSULTATS: Au total, 123 865 cas réalisés dans 11 hôpitaux sur une période de 32 mois ont été passés en revue. Une très faible proportion de patients (753 des 123 865 cas, 0,6 %) sont entrés plus de 90 min plus tôt en SOP que leur heure prévue. Relativement peu de cas ont été effectivement annulés en raison d'une consommation inappropriée de liquides, selon les souvenirs des anesthésiologistes de deux établissements. CONCLUSION: Dans le réseau FHA, le programme opératoire de SOP est un guide fiable pour fournir des instructions quant au moment de consommation préopératoire de liquides chez les patients de chirurgie non urgente sélectionnés. La qualité des soins et la satisfaction des patients seront améliorés en toute sécurité en limitant la période de jeûne pour les patients de chirurgie non urgente.

Evaluating NeuroSENSE for assessing depth of hypnosis during desflurane anesthesia: an adaptive, randomized-controlled trial.

PURPOSE: Processed electroencephalography (EEG) monitors support depth-of-hypnosis assessment during anesthesia. This randomized-controlled trial investigated the performance of the NeuroSENSE electroencephalography (EEG) monitor to determine whether its wavelet anesthetic value for central nervous system (WAVCNS) index distinguishes consciousness from unconsciousness during induction of anesthesia (as assessed by the anesthesiologist) and emergence from anesthesia (indicated by patient responsiveness), and whether it correlates with changes in desflurane minimum alveolar concentration (MAC) during maintenance of anesthesia. METHODS: EEG was collected using a fronto-temporal bilateral montage. The WAVCNS was continuously recorded by the NeuroSENSE monitor, to which the anesthesiologist was blinded. Anesthesia was induced with propofol/remifentanil and maintained with desflurane, with randomized changes of -0.4, 0, or +0.4 MAC every 7.5 min within the 0.8-1.6 MAC range, if clinically acceptable to the anesthesiologist. During emergence from anesthesia, desflurane was stepped down by 0.2 MAC every five minutes. RESULTS: Data from 75 patients with a median [interquartile range] age of 41[35-52] yr were obtained. The WAVCNS distinguished consciousness from unconsciousness as assessed by the anesthesiologist, with area under the receiver operating characteristic curve of 99.5% (95% confidence interval [CI], 98.5 to 100.0) at loss of consciousness and 99.4% (95% CI, 98.5 to 100.0) at return of consciousness. Bilateral WAVCNS changes correlated with desflurane concentrations, with -8.0 and -8.6 WAVCNS units, respectively, per 1 MAC change in the 0.8-1.6 MAC range during maintenance of anesthesia and -10.0 and -10.5 WAVCNS units, respectively, in the 0.4-1.6 MAC range including emergence from anesthesia. CONCLUSION: The NeuroSENSE monitor can reliably discriminate between consciousness and unconsciousness, as assessed by the anesthesiologist, during induction of anesthesia and with a lower level of reliability during emergence from anesthesia. The WAVCNS correlates with desflurane concentration but plateaus at higher concentrations, similar to other EEG monitors, which suggests limited utility to titrate higher concentrations of anesthetic vapour. TRIAL REGISTRATION: clinicaltrials.gov, NCT02088671; registered 17 March, 2014.

Zero-heat-flux core temperature monitoring system: an observational secondary analysis to evaluate agreement with naso-/oropharyngeal probe during anesthesia.

General anesthesia impairs thermoregulation and contributes to perioperative hypothermia; core body temperature monitoring is recommended during surgical procedures lasting > 30 min. Zero-heat-flux core body temperature measurement systems enable continuous non-invasive perioperative monitoring. During a previous trial evaluating the benefits of preoperative forced-air warming, intraoperative temperatures were measured with both a zero-heat-flux sensor and a standard naso-/oropharyngeal temperature probe. The aim of this secondary analysis is to evaluate their agreement. ASA I-III patients, scheduled for elective, non-cardiac surgery under general anesthesia, were enrolled. A zero-heat-flux sensor was placed on the participant's forehead preoperatively. Following induction of anesthesia, a "clinical" temperature probe was placed in the nasopharynx or oropharynx at the anesthesiologist's discretion. Temperature measurements from both sensors were recorded every 10 s. Agreement was analyzed using the Bland-Altman method, corrected for repeated measurements, and Lin's concordance correlation coefficient, and compared with existing studies. Data were collected in 194 patients with a median (interquartile range) age of 60 (49-69) years, during surgical procedures lasting 120 (89-185) min. The zero-heat-flux measurements had a mean bias of - 0.05 °C (zero-heat-flux lower) with 95% limits of agreement within - 0.68 to + 0.58 °C. Lin's concordance correlation coefficient was 0.823. The zero-heat-flux sensor demonstrated moderate agreement with the naso-/oropharyngeal temperature probe, which was not fully within the generally accepted ± 0.5 °C limit. This is consistent with previous studies. The zero-heat-flux system offers clinical utility for non-invasive and continuous core body temperature monitoring throughout the perioperative period using a single sensor.

Effect of preoperative warming on intraoperative hypothermia: a randomized-controlled trial.

PURPOSE: The purpose of this study was to evaluate the effects of preoperative forced-air warming on intraoperative hypothermia. METHODS: In this randomized-controlled trial, adult patients scheduled for elective, non-cardiac surgery under general anesthesia were stratified by scheduled surgical duration (< 2.5 hr or ≥ 2.5 hr) and then randomized to a pre-warming group using a BairPaws™ forced-air warming system for at least 30 min preoperatively or to a control group with warmed blankets on request. All patients were warmed intraoperatively via convective forced-air warming blankets. Perioperative temperature was measured using the SpotOn™ temperature system consisting of a single-use disposable sensor applied to the participant's forehead. The primary outcome was the magnitude of intraoperative hypothermia calculated as the area under the time-temperature curve for core temperatures < 36°C between induction of general anesthesia and leaving the operating room. Secondary outcomes included surgical site infections, packed red blood cell requirements, and 24 hr postoperative opioid consumption. RESULTS: Two hundred participants were analyzed (101 control; 99 pre-warmed). Pre-warmed participants had a lower median [interquartile range] magnitude of hypothermia than controls (0.00 [0.00-0.12] °C·hr-1 vs 0.05 [0.00-0.36] °C·hr-1, respectively; median difference, -0.01°C·hr-1; 95% confidence interval, -0.04 to 0.00°C·hr-1; P = 0.005). There were no between-group differences in the secondary outcomes. CONCLUSION: A minimum of 30 min of preoperative forced-air convective warming decreased the overall intraoperative hypothermic exposure. While redistribution hypothermia still occurs despite pre- and intraoperative forced-air warming, their combined application results in greater preservation of intraoperative normothermia compared with intraoperative forced-air warming alone. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02177903). Registered 25 June 2014.

Design and Evaluation of a Closed-Loop Anesthesia System With Robust Control and Safety System.

BACKGROUND: Closed-loop control of anesthesia involves continual adjustment of drug infusion rates according to measured clinical effect. The NeuroSENSE monitor provides an electroencephalographic measure of depth of hypnosis (wavelet-based anesthetic value for central nervous system monitoring [WAVCNS]). It has previously been used as feedback for closed-loop control of propofol, in a system designed using robust control engineering principles, which implements features specifically designed to ensure patient safety. Closed-loop control of a second drug, remifentanil, may be added to improve WAVCNS stability in the presence of variable surgical stimulation. The objective of this study was to design and evaluate the feasibility of a closed-loop system for robust control of propofol and remifentanil infusions using WAVCNS feedback, with an infusion safety system based on the known pharmacological characteristics of these 2 drugs. METHODS: With Health Canada authorization, research ethics board approval, and informed consent, American Society of Anesthesiologists I-III adults, requiring general anesthesia for elective surgery, were enrolled in a 2-phase study. In both phases, infusion of propofol was controlled in closed loop during induction and maintenance of anesthesia, using WAVCNS feedback, but bounded by upper- and lower-estimated effect-site concentration limits. In phase I, remifentanil was administered using an adjustable target-controlled infusion and a controller was designed based on the collected data. In phase II, remifentanil was automatically titrated to counteract rapid increases in WAVCNS. RESULTS: Data were analyzed for 127 patients, of median (range) age 64 (22-86) years, undergoing surgical procedures lasting 105 (9-348) minutes, with 52 participating in phase I and 75 in phase II. The overall control performance indicator, global score, was a median (interquartile range) 18.3 (14.2-27.7) in phase I and 14.6 (11.6-20.7) in phase II (median difference, -3.25; 95% confidence interval, -6.35 to -0.52). The WAVCNS was within ±10 of the setpoint for 84.3% (76.6-90.6) of the maintenance of anesthesia in phase I and 88.2% (83.1-93.4) in phase II (median difference, 3.7; 95% confidence interval, 0.1-6.9). The lower propofol safety bound was activated during 30 of 52 (58%) cases in phase I and 51 of 75 (68%) cases in phase II. CONCLUSIONS: Adding closed-loop control of remifentanil improved overall controller performance. This controller design offers a robust method to optimize the control of 2 drugs using a single sensor. The infusion safety system is an important component of a robust automated anesthesia system, but further research is required to determine the optimal constraints for these safe conditions.

Closed-Loop Control of Total Intravenous Anesthesia During Significant Intraoperative Blood Loss: A Case Report.

Closed-loop control of anesthesia based on continuous feedback from processed electroencephalography adjusts drug dosing to target a desired depth of hypnosis during dynamic clinical circumstances, freeing the anesthesiologist to focus on more complex tasks. We describe a case of closed-loop control of total intravenous anesthesia in which a sudden loss of blood required immediate intervention. This case illustrates that closed-loop control of drug delivery maintained an appropriate depth of hypnosis during a rapidly changing surgical situation, and that processed electroencephalography may be a useful adjunct indicator for cerebral hypoperfusion.

Nitrous oxide and serious morbidity and mortality in the POISE trial.

BACKGROUND: In this post hoc subanalysis of the Perioperative Ischemic Evaluation (POISE) trial, we sought to determine whether nitrous oxide was associated with the primary composite outcome of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal cardiac arrest within 30 days of randomization. METHODS: The POISE trial of perioperative ß-blockade was undertaken in 8351 patients. Nitrous oxide anesthesia was defined as the coadministration of nitrous oxide in patients receiving general anesthesia, with or without additional neuraxial blockade or peripheral nerve blockade. Logistic regression, with inverse probability weighting using estimated propensity scores, was used to determine the association of nitrous oxide with the primary outcome, MI, stroke, death, and clinically significant hypotension. RESULTS: Nitrous oxide was administered to 1489 (29%) of the 5133 patients included in this analysis. Nitrous oxide had no significant effect on the risk of the primary outcome (112 [7.5%] vs 248 [6.9%]; odds ratio [OR], 1.08; 95% confidence interval [CI], 0.82-1.44; 99% CI, 0.75-1.57; P = 0.58), MI (89 [6.0] vs 204 [5.6]; OR, 0.99; 95% CI, 0.75-1.31; 99% CI, 0.69-1.42; P = 0.94), stroke (6 [0.4%] vs 28 [0.8%]; OR, 0.85; 95% CI, 0.26-2.82; 99% CI, 0.17-4.11; P = 0.79), death (40 [2.7%] vs 100 [2.8%]; OR, 1.04; 95% CI, 0.6-1.81; 99% CI, 0.51-2.15; P = 0.88) or clinically significant hypotension (219 [14.7%] vs 544 [15.0%]; OR, 0.92; 95% CI, 0.74-1.15; 99% CI, 0.70-1.23; P = 0.48). CONCLUSIONS: In this post hoc subanalysis, nitrous oxide was not associated with an increased risk of adverse outcomes in the POISE trial patients. This analysis was limited by the observational nature of the data and the lack of information on the concentration and duration of nitrous oxide administration. Further randomized controlled trial evidence is required.