Animal studies on ketamine and opioid tolerance have shown promising results. Clinical trials have been contradictory. We performed a systematic review of randomized, double-blind clinical trials of ketamine added to opioid analgesia. Thirty-seven trials with 51 treatment arms and 2385 patients were included. Studies were divided into 5 subgroups: IV ketamine as single dose (n = 11), continuous infusion (n = 11), patient-controlled analgesia (PCA) (n = 6), epidural ketamine with opioids (n = 8), and studies in children (n = 4). Outcome measures included pain scores, time to first request for analgesia, supplemental analgesics, and adverse events. Efficacy was estimated by statistical significance (P < 0.05) of outcome measures as reported in studies and also by calculation of weighted mean difference for pain scores during the first 24 h after surgery. As compared to morphine alone, IV PCA with ketamine and morphine did not improve analgesia. Intravenous infusion of ketamine decreased IV and epidural opioid requirements in 6 of 11 studies. A single bolus dose of ketamine decreased opioid requirements in 7 of 11 studies. Five of 8 trials with epidural ketamine showed beneficial effects. Adverse effects were not increased with small dose ketamine. We conclude that small dose ketamine is a safe and useful adjuvant to standard practice opioid-analgesia.
IMPORTANCEPostoperative delirium is common following cardiac surgery and may be affected by choice of analgesic and sedative.OBJECTIVE To evaluate the effect of postoperative intravenous (IV) acetaminophen (paracetamol) vs placebo combined with IV propofol vs dexmedetomidine on postoperative delirium among older patients undergoing cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS Randomized, placebo-controlled, factorial clinical trial among 120 patients aged 60 years or older undergoing on-pump coronary artery bypass graft (CABG) surgery or combined CABG/valve surgeries at a US center. Enrollment was September 2015 to April 2018, with follow-up ending in April 2019.INTERVENTIONS Patients were randomized to 1 of 4 groups receiving postoperative analgesia with IV acetaminophen or placebo every 6 hours for 48 hours and postoperative sedation with dexmedetomidine or propofol starting at chest closure and continued for up to 6 hours (acetaminophen and dexmedetomidine: n = 29; placebo and dexmedetomidine: n = 30; acetaminophen and propofol: n = 31; placebo and propofol: n = 30). MAIN OUTCOMES AND MEASURESThe primary outcome was incidence of postoperative in-hospital delirium by the Confusion Assessment Method. Secondary outcomes included delirium duration, cognitive decline, breakthrough analgesia within the first 48 hours, and ICU and hospital length of stay. RESULTS Among 121 patients randomized (median age, 69 years; 19 women [15.8%]), 120 completed the trial. Patients treated with IV acetaminophen had a significant reduction in delirium (10% vs 28% placebo; difference, −18% [95% CI, −32% to −5%]; P = .01; HR, 2.8 [95% CI, 1.1-7.8]). Patients receiving dexmedetomidine vs propofol had no significant difference in delirium (17% vs 21%; difference, −4% [95% CI, −18% to 10%]; P = .54; HR, 0.8 [95% CI, 0.4-1.9]). There were significant differences favoring acetaminophen vs placebo for 3 prespecified secondary outcomes: delirium duration (median, 1 vs 2 days; difference, −1 [95% CI, −2 to 0]), ICU length of stay (median, 29.5 vs 46.7 hours; difference, −16.7 [95% CI, −20.3 to −0.8]), and breakthrough analgesia (median, 322.5 vs 405.3 μg morphine equivalents; difference, −83 [95% CI, −154 to −14]). For dexmedetomidine vs propofol, only breakthrough analgesia was significantly different (median, 328.8 vs 397.5 μg; difference, −69 [95% CI, −155 to −4]; P = .04). Fourteen patients in both the placebo-dexmedetomidine and acetaminophen-propofol groups (46% and 45%) and 7 in the acetaminophendexmedetomidine and placebo-propofol groups (24% and 23%) had hypotension.CONCLUSIONS AND RELEVANCE Among older patients undergoing cardiac surgery, postoperative scheduled IV acetaminophen, combined with IV propofol or dexmedetomidine, reduced in-hospital delirium vs placebo. Additional research, including comparison of IV vs oral acetaminophen and other potentially opioid-sparing analgesics, on the incidence of postoperative delirium is warranted.
We performed a retrospective review of a vascular surgery quality assurance database to evaluate the perioperative and long-term morbidity and mortality of above-knee amputations (AKA, n = 234) and below-knee amputations (BKA, n = 720) and to examine the effect of diabetes mellitus (DM) (181 of AKA and 606 of BKA patients). All patients in the database who had AKA or BKA from 1990 to May 2001 were included in the study. Perioperative 30-day cardiac morbidity and mortality and 3-yr and 10-yr mortality after AKA or BKA were assessed. The effect of DM on 30-day cardiac outcome was assessed by multivariate logistic regression and the effect on long-term survival was assessed by Cox regression analysis. The perioperative cardiac event rate (cardiac death or nonfatal myocardial infarction) was at least 6.8% after AKA and at most 3.6% after BKA. Median survival was significantly less after AKA (20 mo) than BKA (52 mo) (P < 0.001). DM was not a significant predictor of perioperative 30-day mortality (odds ratio, 0.76 [0.39-1.49]; P = 0.43) or 3-yr survival (Hazard ratio, 1.03 [0.86-1.24]; P = 0.72) but predicted 10-yr mortality (Hazard ratio, 1.34 [1.04-1.73]; P = 0.026). Significant predictors of the 30-day perioperative mortality were the site of amputation (odds ratio, 4.35 [2.56-7.14]; P < 0.001) and history of renal insufficiency (odds ratio, 2.15 [1.13-4.08]; P = 0.019). AKA should be triaged as a high-risk surgery while BKA is an intermediate-risk surgery. Long-term survival after AKA or BKA is poor, regardless of the presence of DM.
The presence of perioperative diastolic dysfunction as assessed with Vp is an independent predictor of postoperative CHF and prolonged length of stay after major vascular surgery. Patient age, gender, type of surgery, and renal failure were also predictors of outcome. Perioperative systolic function was not a predictor of postoperative outcome in our patients.
Postoperative glycemic variability is associated with MAEs after cardiac surgery. Glycemic variability is only measured when the patient leaves the intensive care unit, and there is no opportunity to intervene earlier. Preoperative HbA1C identifies risk for postoperative glycemic variability and may provide a more rational guide for targeting measures to reduce variability.
Continuous insulin infusion reduces perioperative myocardial infarction after vascular surgery.
Background Despite evidence suggesting detrimental effects of perioperative hyperoxia, hyperoxygenation remains commonplace in cardiac surgery. Hyperoxygenation may increase oxidative damage and neuronal injury leading to potential differences in postoperative neurocognition. Therefore, this study tested the primary hypothesis that intraoperative normoxia, as compared to hyperoxia, reduces postoperative cognitive dysfunction in older patients having cardiac surgery. Methods A randomized double-blind trial was conducted in patients aged 65 yr or older having coronary artery bypass graft surgery with cardiopulmonary bypass. A total of 100 patients were randomized to one of two intraoperative oxygen delivery strategies. Normoxic patients (n = 50) received a minimum fraction of inspired oxygen of 0.35 to maintain a Pao2 above 70 mmHg before and after cardiopulmonary bypass and between 100 and 150 mmHg during cardiopulmonary bypass. Hyperoxic patients (n = 50) received a fraction of inspired oxygen of 1.0 throughout surgery, irrespective of Pao2 levels. The primary outcome was neurocognitive function measured on postoperative day 2 using the Telephonic Montreal Cognitive Assessment. Secondary outcomes included neurocognitive function at 1, 3, and 6 months, as well as postoperative delirium, mortality, and durations of mechanical ventilation, intensive care unit stay, and hospital stay. Results The median age was 71 yr (interquartile range, 68 to 75), and the median baseline neurocognitive score was 17 (16 to 19). The median intraoperative Pao2 was 309 (285 to 352) mmHg in the hyperoxia group and 153 (133 to 168) mmHg in the normoxia group (P < 0.001). The median Telephonic Montreal Cognitive Assessment score on postoperative day 2 was 18 (16 to 20) in the hyperoxia group and 18 (14 to 20) in the normoxia group (P = 0.42). Neurocognitive function at 1, 3, and 6 months, as well as secondary outcomes, were not statistically different between groups. Conclusions In this randomized controlled trial, intraoperative normoxia did not reduce postoperative cognitive dysfunction when compared to intraoperative hyperoxia in older patients having cardiac surgery. Although the optimal intraoperative oxygenation strategy remains uncertain, the results indicate that intraoperative hyperoxia does not worsen postoperative cognition after cardiac surgery. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
BackgroundDelirium is associated with a significantly increased risk of postoperative morbidity and mortality. Furthermore, delirium has been associated with an increased risk of prolonged cognitive deficits and accelerated long-term cognitive decline. To date, experimental interventions for delirium have mainly focused on alternative pharmacologic and behavioral strategies in the postoperative period. Few studies have examined whether proactive strategies started before surgery can prevent delirium or reduce its sequelae. Neurocognitive training programs such as Lumosity have been shown to be effective in increasing cognitive performance in both elderly healthy volunteers and patients suffering from a myriad of acute and chronic medical conditions. When initiated in the preoperative period, such training programs may serve as interesting and novel patient-led interventions for the prevention of delirium and postoperative cognitive decline (POCD). We hypothesize that perioperative neurocognitive training is feasible in the older cardiac surgical population and are testing this hypothesis using a randomized controlled design.MethodsThe Prevention of Early Postoperative Decline (PEaPoD) study is a randomized, controlled trial with a target enrollment of 45 elderly cardiac surgical patients. Subjects will be randomized in a 1:1 ratio to undergo either at least 10 days of preoperative neurocognitive training, continued for 4 weeks postoperatively, or usual care control. The primary outcome, feasibility, will be assessed by study recruitment and adherence to protocol. Secondary outcomes will include potential differences in the incidence of postoperative in-hospital delirium and POCD up to 6 months, as determined by the Confusion Assessment Method and the Montreal Cognitive Assessment.DiscussionPEaPoD will be the first trial investigating the use of perioperative cognitive training to potentially reduce delirium and POCD in the cardiac surgical population. Information gleaned from this feasibility study will prove valuable in designing future efficacy studies aimed at determining whether this low-risk, patient-led intervention can reduce serious postoperative morbidity.Trial registrationClinicalTrials.gov, NCT02908464. Registered on 21 September 2016.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-3063-z) contains supplementary material, which is available to authorized users.
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