Sherry L. McKinnon

Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial

Background Delirium and pain are common and serious postoperative complications. Subanaesthetic ketamine is often administered intraoperatively for postoperative analgesia and to spare postoperative opioids. Some evidence also suggests that ketamine prevents delirium. The primary purpose of this trial was to evaluate the effectiveness of ketamine in preventing postoperative delirium in older adults after major surgery. Secondary outcomes, viewed as strongly related to delirium, were postoperative pain and opioid consumption. Methods This was a multicentre, international, randomised trial that enrolled adults older than 60 undergoing major cardiac and noncardiac surgery under general anaesthesia. Participants were enrolled prior to surgery and gave written informed consent. We used a computer-generated randomisation sequence. Patients at study sites were randomised to one of three study groups in blocks of 15 to receive intraoperative administration of (i) placebo (intravenous normal saline), (ii) low dose ketamine (0.5 mg/kg) or (iii) high dose ketamine (1 mg/kg). Study drug was administered following induction of anaesthesia, prior to surgical incision. Participants, clinicians, and investigators were all masked to group assignment. Delirium and pain were assessed twice daily in the first three postoperative days using the Confusion Assessment Method and Visual Analog Scale, respectively. Postoperative opioid use was recorded, and hallucinations and nightmares were assessed. Analyses were performed by intention-to-treat and adverse events were evaluated. The Prevention of Delirium and Complications Associated with Surgical Treatments [PODCAST] trial is registered in clinicaltrials.gov; NCT01690988 Findings Between February 6, 2014 and June 26, 2016, 1360 patients assessed and 672 were randomised, with 222 in the placebo group, 227 in the low dose ketamine group, and 223 in the high dose ketamine group. There was no difference in postoperative delirium incidence between those in the combined ketamine groups and those who received placebo (19.45% vs. 19.82%, respectively; absolute difference, 0.36%; 95% CI, −6.07% to 7.38%; p=0.92). There were no significant differences among the three groups in maximum pain scores (p=0.88) or median opioid consumption (p=0.47) over time. There were more postoperative hallucinations (p=0.01) and nightmares (p=0.03) with escalating doses of ketamine. Adverse events (cardiovascular, renal, infectious, gastrointestinal, bleeding), whether viewed individually (P value for each >0.40) or collectively (82/222 [36.9%] in placebo group, 90/227 [39.6%] in low dose ketamine group, 91/223 in high dose ketamine group [40.8%]; P=0.69), did not differ significantly across the three groups. Interpretation The administration of a single subanaesthetic dose of ketamine to older adults during major surgery did not show evidence of reducing postoperative delirium, pain, or opioid consumption, and might cause harm by inducing negative experiences. Given current evidence and guidelines related to ketamine and postoperative analgesia, the unexpected secondary findings regarding pain and opioid consumption warrant replication or refutation in subsequent research. Funding The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The principal investigators (MSA and GAM) had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Protocol for the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) study: a pragmatic, randomised clinical trial

Introduction Postoperative delirium, arbitrarily defined as occurring within 5 days of surgery, affects up to 50% of patients older than 60 after a major operation. This geriatric syndrome is associated with longer intensive care unit and hospital stay, readmission, persistent cognitive deterioration and mortality. No effective preventive methods have been identified, but preliminary evidence suggests that EEG monitoring during general anaesthesia, by facilitating reduced anaesthetic exposure and EEG suppression, might decrease incident postoperative delirium. This study hypothesises that EEG-guidance of anaesthetic administration prevents postoperative delirium and downstream sequelae, including falls and decreased quality of life. Methods and analysis This is a 1232 patient, block-randomised, double-blinded, comparative effectiveness trial. Patients older than 60, undergoing volatile agent-based general anaesthesia for major surgery, are eligible. Patients are randomised to 1 of 2 anaesthetic approaches. One group receives general anaesthesia with clinicians blinded to EEG monitoring. The other group receives EEG-guidance of anaesthetic agent administration. The outcomes of postoperative delirium (≤5 days), falls at 1 and 12 months and health-related quality of life at 1 and 12 months will be compared between groups. Postoperative delirium is assessed with the confusion assessment method, falls with ProFaNE consensus questions and quality of life with the Veterans RAND 12-item Health Survey. The intention-to-treat principle will be followed for all analyses. Differences between groups will be presented with 95% CIs and will be considered statistically significant at a two-sided p<0.05. Ethics and dissemination Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) is approved by the ethics board at Washington University. Recruitment began in January 2015. Dissemination plans include presentations at scientific conferences, scientific publications, internet-based educational materials and mass media. Trial registration number NCT02241655; Pre-results.

Methodologic Considerations for Collecting Patient-reported Outcomes from Unselected Surgical Patients

Background:The impact of surgery on health is only appreciated long after hospital discharge. Furthermore, patients’ perceptions of postoperative health are not routinely ascertained. The authors instituted the Systematic Assessment and Targeted Improvement of Services Following Yearlong Surgical Outcomes Surveys (SATISFY-SOS) registry to evaluate patients’ postoperative health based on patient-reported outcomes (PROs). Methods:This article describes the methods of establishing the SATISFY-SOS registry from an unselected surgical population, combining perioperative PROs with information from electronic medical records. Patients enrolled during their preoperative visit were surveyed at enrollment, 30 days, and 1-yr postoperatively. Information on PROs, including quality of life, return to work, pain, functional status, medical complications, and cognition, was obtained from online, mail, or telephone surveys. Results:Using structured query language, 44,081 patients were identified in the electronic medical records as having visited the Center for Preoperative Assessment and Planning for preoperative assessment between July 16, 2012, and June 15, 2014, and 20,719 patients (47%) consented to participate in SATISFY-SOS. Baseline characteristics and health status were similar between enrolled and not enrolled patients. The response rate for the 30-day survey was 62% (8% e-mail, 73% mail, and 19% telephone) and for the 1-yr survey was 71% (13% e-mail, 78% mail, and 8% telephone). Conclusions:SATISFY-SOS demonstrates the feasibility of establishing a PRO registry reflective of a busy preoperative assessment center population, without disrupting clinical workflow. Our experience suggests that patient engagement, including informed consent and multiple survey modalities, enhances PROs collection from a large cohort of unselected surgical patients. Initiatives like SATISFY-SOS could promote quality improvement, enable efficient perioperative research, and facilitate outcomes that matter to surgical patients.

Preoperative Falls Predict Postoperative Falls, Functional Decline, and Surgical Complications

Background Falls are common and linked to morbidity. Our objectives were to characterize postoperative falls, and determine whether preoperative falls independently predicted postoperative falls (primary outcome), functional dependence, quality of life, complications, and readmission. Methods This prospective cohort study included 7982 unselected patients undergoing elective surgery. Data were collected from the medical record, a baseline survey, and follow-up surveys approximately 30 days and one year after surgery. Results Fall rates (per 100 person-years) peaked at 175 (hospitalization), declined to 140 (30-day survey), and then to 97 (one-year survey). After controlling for confounders, a history of one, two, and ≥ three preoperative falls predicted postoperative falls at 30 days (adjusted odds ratios [aOR] 2.3, 3.6, 5.5) and one year (aOR 2.3, 3.4, 6.9). One, two, and ≥ three falls predicted functional decline at 30 days (aOR 1.2, 2.4, 2.4) and one year (aOR 1.3, 1.5, 3.2), along with in-hospital complications (aOR 1.2, 1.3, 2.0). Fall history predicted adverse outcomes better than commonly-used metrics, but did not predict quality of life deterioration or readmission. Conclusions Falls are common after surgery, and preoperative falls herald postoperative falls and other adverse outcomes. A history of preoperative falls should be routinely ascertained.

Preoperative Falls and Their Association with Functional Dependence and Quality of Life.

Background:No study has rigorously explored the characteristics of surgical patients with recent preoperative falls. Our objective was to describe the essential features of preoperative falls and determine whether they are associated with preoperative functional dependence and poor quality of life. Methods:This was an observational study involving 15,060 surveys from adult patients undergoing elective surgery. The surveys were collected between January 2014 and August 2015, with a response rate of 92%. Results:In the 6 months before surgery, 26% (99% CI, 25 to 27%) of patients fell at least once, and 12% (99% CI, 11 to 13%) fell at least twice. The proportion of patients who fell was highest among patients presenting for neurosurgery (41%; 99% CI, 36 to 45%). At least one fall-related injury occurred in 58% (99% CI, 56 to 60%) of those who fell. Falls were common in all age groups, but surprisingly, they did not increase monotonically with age. Middle-aged patients (45 to 64 yr) had the highest proportion of fallers (28%), recurrent fallers (13%), and severe fall-related injuries (27%) compared to younger (18 to 44 yr) and older (65+ yr) patients (P < 0.001 for each). A fall within 6 months was independently associated with preoperative functional dependence (odds ratio, 1.94; 99% CI, 1.68 to 2.24) and poor physical quality of life (odds ratio, 2.18; 99% CI, 1.88 to 2.52). Conclusions:Preoperative falls might be common and are possibly often injurious in the presurgical population, across all ages. A history of falls could enhance the assessment of preoperative functional dependence and quality of life.

Convergent Validity of Three Methods for Measuring Postoperative Complications

Background:Anesthesiologists need tools to accurately track postoperative outcomes. The accuracy of patient report in identifying a wide variety of postoperative complications after diverse surgical procedures has not previously been investigated. Methods:In this cohort study, 1,578 adult surgical patients completed a survey at least 30 days after their procedure asking if they had experienced any of 18 complications while in the hospital after surgery. Patient responses were compared to the results of an automated electronic chart review and (for a random subset of 750 patients) to a manual chart review. Results from automated chart review were also compared to those from manual chart review. Forty-two randomly selected patients were contacted by telephone to explore reasons for discrepancies between patient report and manual chart review. Results:Comparisons between patient report, automated chart review, and manual chart review demonstrated poor-to-moderate positive agreement (range, 0 to 58%) and excellent negative agreement (range, 82 to 100%). Discordance between patient report and manual chart review was frequently explicable by patients reporting events that happened outside the time period of interest. Conclusions:Patient report can provide information about subjective experiences or events that happen after hospital discharge, but often yields different results from chart review for specific in-hospital complications. Effective in-hospital communication with patients and thoughtful survey design may increase the quality of patient-reported complication data.

Changes in quality of life after elective surgery: an observational study comparing two measures

PurposeOur main objective was to compare the change in a validated quality of life measure to a global assessment measure. The secondary objectives were to estimate the minimum clinically important difference (MCID) and to describe the change in quality of life by surgical specialty.MethodsThis prospective cohort study included 7902 adult patients undergoing elective surgery. Changes in the Veterans RAND 12-Item Health Survey (VR-12), composed of a physical component summary (PCS) and a mental component summary (MCS), were calculated using preoperative and postoperative questionnaires. The latter also contained a global assessment question for quality of life. We compared PCS and MCS to the global assessment using descriptive statistics and weighted kappa. MCID was calculated using an anchor-based approach. Analyses were pre-specified and registered (NCT02771964).ResultsBy the change in VR-12 scores, an equal proportion of patients experienced improvement and deterioration in quality of life (28% for PCS, 25% for MCS). In contrast, by the global assessment measure, 61% reported improvement, while only 10% reported deterioration. Agreement with the global assessment was slight for both PCS (kappa = 0.20, 57% matched) and MCS (kappa = 0.10, 54% matched). The MCID for the overall VR-12 score was approximately 2.5 points. Patients undergoing orthopedic surgery showed the most improvement in quality of life measures, while patients undergoing gastrointestinal/hepatobiliary or urologic surgery showed the most deterioration.ConclusionsSubjective global quality of life report does not agree well with a validated quality of life instrument, perhaps due to patient over-optimism.

Ability of preoperative falls to predict postsurgical outcomes in non-selected patients undergoing elective surgery at an academic medical centre: protocol for a prospective cohort study

Introduction Falls are increasingly recognised for their ability to herald impending health decline. Despite the likely susceptibility of postsurgical patients to falls, a detailed description of postoperative falls in an unselected surgical population has never been performed. One study suggests that preoperative falls may forecast postoperative complications. However, a larger study with non-selected surgical patients and patient-centred outcomes is needed to provide the generalisability and justification necessary to implement preoperative falls assessment into routine clinical practice. The aims of this study are therefore twofold. First, we aim to describe the main features of postoperative falls in a population of unselected surgical patients. Second, we aim to test the hypothesis that a history of falls in the 6 months prior to surgery predicts postoperative falls, poor quality of life, functional dependence, complications and readmission. Methods and analysis To achieve these goals, we study adult patients who underwent elective surgery at our academic medical centre and were recruited to participate in a prospective, survey-based cohort study called Systematic Assessment and Targeted Improvement of Services Following Yearlong Surgical Outcomes Surveys (SATISFY-SOS) (NCT02032030). Patients who reported falling in the 6 months prior to surgery will be considered ‘exposed.’ The primary outcome of interest is postoperative falls within 30 days of surgery. Secondary outcomes include postoperative functional dependence, quality of life (both physical and mental), in-hospital complications and readmission. Regression models will permit controlling for important confounders. Ethics and dissemination The home institutions Institutional Review Board approved this study (IRB ID number 201505035). The authors will publish the findings, regardless of the results.

Protocol for an observational study of delirium in the post-anaesthesia care unit (PACU) as a potential predictor of subsequent postoperative delirium

Introduction Postoperative delirium can be a serious consequence of major surgery, associated with longer hospital stays, readmission, cognitive and functional deterioration and mortality. Delirium is an acute, reversible disorder characterised by fluctuating course, inattention, disorganised thinking and altered level of consciousness. Delirium occurring in the hours immediately following anaesthesia and delirium occurring in the postoperative period of 1–5 days have been described as distinct clinical entities. This protocol describes an observational study with the aim of determining if delirium in the first hour following tracheal tube removal is a predictor of delirium in the 5 subsequent postoperative days. Improved understanding regarding the development of postoperative delirium would improve patient care and allow more effective implementation of delirium prevention measures. Methods and analysis Patients enrolled to the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) randomised controlled trial will be eligible for this substudy. A validated delirium assessment method, the 3-min Diagnostic Confusion Assessment Method and the Richmond Agitation and Sedation Scale will be used to assess 100 patients for delirium at 30 min and 60 min following tracheal tube removal. Patients will also be assessed for delirium over postoperative days 1–5 using three validated methods, the Confusion Assessment Method (CAM), CAM for the Intensive Care Unit and structured chart review. Logistic regression analysis will then be performed to test whether immediately postoperative delirium independently predicts subsequent postoperative delirium. Ethics and dissemination This observational substudy of ENGAGES has been approved by the ethics board of Washington University School of Medicine. Enrolment began in June 2016 and will continue until June 2017. Dissemination plans include presentations at scientific conferences and scientific publications. Trial registration number NCT02241655.

Using machine learning techniques to develop forecasting algorithms for postoperative complications: Protocol for a retrospective study

Introduction Mortality and morbidity following surgery are pressing public health concerns in the USA. Traditional prediction models for postoperative adverse outcomes demonstrate good discrimination at the population level, but the ability to forecast an individual patient’s trajectory in real time remains poor. We propose to apply machine learning techniques to perioperative time-series data to develop algorithms for predicting adverse perioperative outcomes. Methods and analysis This study will include all adult patients who had surgery at our tertiary care hospital over a 4-year period. Patient history, laboratory values, minute-by-minute intraoperative vital signs and medications administered will be extracted from the electronic medical record. Outcomes will include in-hospital mortality, postoperative acute kidney injury and postoperative respiratory failure. Forecasting algorithms for each of these outcomes will be constructed using density-based logistic regression after employing a Nadaraya-Watson kernel density estimator. Time-series variables will be analysed using first and second-order feature extraction, shapelet methods and convolutional neural networks. The algorithms will be validated through measurement of precision and recall. Ethics and dissemination This study has been approved by the Human Research Protection Office at Washington University in St Louis. The successful development of these forecasting algorithms will allow perioperative healthcare clinicians to predict more accurately an individual patient’s risk for specific adverse perioperative outcomes in real time. Knowledge of a patient’s dynamic risk profile may allow clinicians to make targeted changes in the care plan that will alter the patient’s outcome trajectory. This hypothesis will be tested in a future randomised controlled trial.