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...

"Inadequate source control and inappropriate antibiotics are key determinants of mortality in patients with intra-abdominal sepsis and associated bacteremia." Surgical Infections. 16,6. 785-793. (2015 Background: Patients with intra-abdominal sepsis and associated bacteremia have a high mortality rate. However, outcomes studies in this population are limited, in part because of the small numbers of such patients. The objective of this study was to describe characteristics of critically ill patients with secondary blood stream infection (BSI) of intra-abdominal origin and identify predictors of mortality.Methods: This retrospective, single-center study evaluated patients admitted between January 2005 and January 2011 with bacteremia because of an intra-abdominal source. Patients were included if they met criteria for severe sepsis based on International Classification of Diseases, 9th Revision (ICD 9) codes for acute organ dysfunction, had a positive blood culture, had at least one ICD 9 code indicative of an intra-abdominal process, and had a confirmed or clinically suspected intra-abdominal infection (IAI) within 72 h of the blood culture. Chart review was performed to confirm the presence of these criteria and also the absence of any other potential source of bacteremia. Data were collected on patient demographics, BSI source, source control procedure details, microorganisms isolated, and antibiotics administered. Multivariable logistic regression analysis was performed to identify independent predictors of mortality. Results: Three hundred six patients with BSI were identified, of which 108 episodes were deemed to be of intraabdominal origin. Gram-negative organisms comprised 43% of blood isolates, followed by gram-positives (33%), anaerobes (14%), and yeast (9%). Appropriate antimicrobial therapy was administered in 71% of patients. The overall mortality rate was 27.8%. As compared with survivors, non-survivors were older, more likely to have underlying COPD or asthma, and have renal or metabolic failure (p < 0.05 for all). Among non-survivors, adequate source control was obtained less frequently (64% vs. 91%, p = 0.002) and median time to appropriate antibiotics was longer (23 h vs. 4 h, p = 0.004). Logistic regression analysis revealed inadequate source control (p = 0.002) and inappropriate antibiotics (p = 0.016) to be independently associated with mortality. Conclusions: Critically ill patients with a BSI of abdominal origin are at high risk for mortality. Failure to achieve adequate source control and administration of inappropriate antibiotics were independent predictors of mortality. Thus, these represent potential opportunities to impact outcomes in patients with complicated IAI.

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The use of ketamine infusion for sedation/analgesia in patients receiving extracorporeal membrane oxygenation (ECMO) therapy has not been described. The aims of this retrospective cohort study were to explore whether ketamine infusion for patients requiring ECMO therapy was associated with altered RASS scores, decreased concurrent sedative or opioid use, or with changes in vasopressor requirements. All patients on ECMO who received ketamine infusions in addition to sedative and/or opioid infusions between December 2013 and October 2014 at Barnes-Jewish Hospital in St. Louis were retrospectively identified. Patient characteristics and process of care data were collected.A total of 26 ECMO patients receiving ketamine infusion were identified. The median (inter quartile range [range]) age was 40 years (30-52 [25-66]) with 62% male. The median starting infusion rate of ketamine was 50 mg/hr (30-50 [6-150]) and it was continued for a median duration of 9 days (4-14 [0.2-21]). Prior to ketamine, 14/26 patients were receiving vasopressor infusions to maintain hemodynamic stability. Ketamine initiation was associated with a decrease in vasopressor requirement in 11/26  patients within two hours, and 0/26 required an increase (p<0.001). All patients were receiving sedative and/or opioid infusions at the time of ketamine initiation; 9/26 had a decrease in these infusions within two hours of ketamine initiation, and 1/26 had an increase (p=0.02; odds ratio for decrease to increase = 9; 95% CI, 1.14 to 71.04). The median (IQR[range]) RASS score 24 hours before ketamine initiation was -4 (-3 to -5, [0 to -5]) and after ketamine was -4 (-3 to -4 [-1 to -5]) ( P = 0.614).Ketamine infusion can be used as an adjunctive sedative agent in patients receiving ECMO and may decrease concurrent sedative and/or opioid infusions without altering RASS scores. The hemodynamic effects of ketamine may provide the benefit of decreasing vasopressor requirements.

Twenty-one percent of dexmedetomidine infusion episodes met the criteria for intolerance/failure. No predictors of intolerance/failure were found to be clinically significant.