Background: Neuropsychiatric complications of surgical coronary revascularization are inconspicuous but frequent and clinically relevant. So far, attempts to reduce their occurrence, such as the introduction of off-pump coronary artery bypass (OPCAB) grafting method, have not brought the desired results. The aim of this trial was to determine whether using any of the 2 selected modifications of OPCAB could decrease the incidence of these undesired sequelae.

Methods: In this single-center, assessor- and patient-blinded, superiority, randomized controlled trial, 192 patients scheduled for elective isolated OPCAB were randomized to 3 parallel arms. The control arm underwent "conventional" OPCAB with vein grafts. The first study arm underwent anaortic OPCAB (ANA) with total arterial revascularization. The second study arm underwent OPCAB with vein grafts using carbon dioxide surgical field flooding (CO₂FF). Outcomes included the incidence of postoperative delirium (PD) and early postoperative cognitive dysfunction (ePOCD).

Results: The incidence of PD was 35.9% in the control (OPCAB) arm, 32.8% in the CO₂FF arm, and 12.5% in the ANA arm (χ² [2, N = 191] = 10.17; P = .006). Post hoc tests revealed that the incidence of PD in the ANA arm differed from that in the OPCAB arm (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.09-0.68; P = .002). The incidence of ePOCD was 34.4% in the OPCAB arm, 28.1% in the CO₂FF arm, and 9.5% in the ANA arm (χ² [2, N = 191] = 11.58; P = .003). Post hoc tests revealed that the incidence of ePOCD differed between the ANA and OPCAB arms (OR, 0.20; 95% CI, 0.06-0.58; P < .001).

Conclusions: Performing ANA significantly decreases the incidence of PD and ePOCD compared with "conventional" OPCAB with vein grafts, whereas CO₂FF is inconsequential in this regard. These results, which probably reflect decreased delivery of embolic load to the brain in ANA, may have practical applicability in daily practice to improve clinical outcomes.

Background: Early mobilization of patients in intensive care units (ICUs) improves patient recovery, but implementation remains challenging. Protocols may enhance the rate of out-of-bed mobilizations.

Aim: To evaluate the effect of implementing a protocol for early mobilization on the rate of out-of-bed mobilizations and other outcomes of ICU patients.

Study design: Multicentre, stepped-wedge, cluster-randomized pilot study.

Methods: After a control period, five ICUs were allocated to the implementation of an inter-professional protocol for early mobilization in a randomized, monthly order. Mobilization of ICU patients was evaluated by monthly 1-day point prevalence surveys using the ICU Mobility Scale. The primary outcome was the percentage of patients mobilized out of bed, defined as level 3 on the ICU Mobility Scale (sitting on edge of bed) or higher. Secondary outcomes were mechanical ventilation, delirium and ICU- and hospital-days, as well as unwanted safety events.

Results: Out-of-bed mobilizations increased non-significantly from 36·2% (n = 55) of 152 patients during the control period to 45·8% (n = 55) of 120 patients during the intervention period (difference 9·6%; 95% confidence interval -2·1 to 21·3%). Of 55 mobilized patients per group, more patients were mobilized once per day during the intervention period (intervention: n = 41 versus control: n = 23 patients). Multiple daily mobilizations decreased (control: n = 32 control versus intervention: n = 14 patients). Secondary outcomes, such as days with mechanical ventilation, delirium and in ICU and hospital, did not significantly differ. Adherence to the protocol was >90%; unwanted safety events were rare.

Conclusions: Implementing a protocol for early mobilization of ICU patients showed a trend towards more patients being mobilized. Without additional staff in participating ICUs, a significant increase in ICU mobilizations was not to be anticipated. More research should address whether more staff would increase the number of frequent mobilizations and if this is relevant to outcomes.

Relevance to clinical practice: Implementing inter-professional protocols for mobilization is feasible and safe and may contribute to an increase of ICU patients mobilized out of bed.

Background: Postoperative delirium (POD) is a common complication after surgery.

Objective: We sought to determine the association between preoperative anticholinergic load calculated using the anticholinergic drug scale (ADS) and POD in cancer patients over 65 years of age.

Design: A retrospective sub-investigation of a randomised controlled interventional trial.

Setting: Two tertiary university hospitals.

Patients: Overall, patients aged 65 years and older scheduled for surgical treatment of gastrointestinary, genitourinary or gynaecological cancers.

Main outcome measures: The primary outcome was the interaction between anticholinergic drug scale and occurrence of postoperative delirium. Patient clinical parameters and ADS scores were assessed preoperatively. POD screening was conducted for a total of 7 days following surgery using validated measures. Independent associations between ADS and POD were assessed using multivariate logistical regression analyses.

Results: A total of 651 patients (mean age, 71.8 years; 68.5% males) were included. Of those, 66 patients (10.1%) developed POD. The ADS score was independently associated with the occurrence of POD (higher ADS per point OR 1.496; 95% CI 1.09-2.05; p = 0.01). Additionally, age (per year OR 1.06; CI 95% CI 1.01-1.11; p = 0.03) and ASA state (OR 2.16; 95% CI 1.22-3.83; p = 0.01), as well as stay on ICU (yes vs. no OR 2.8; 95% CI 1.57-4.998; p < 0.01), were independently associated with POD.

Conclusions: ADS assessment according to chronic medication use is a cost-effective, non-invasive method of identifying elderly cancer patients at risk for POD.

Trial registry: www.clinicaltrials.gov. Identifier NCT01278537. Ethics: IRB of Charité University-Medicine Berlin, Germany; EA2/241/08.

Study objective: Postoperative delirium occurs in 20-50% of elderly patients undergoing cardiac surgery and increases morbidity and mortality. We investigated whether prophylactic dexmedetomidine could reduce delirium incidence in elderly patients after coronary artery bypass grafting (CABG), compared with clonidine.

Design: Prospective observational trial.

Setting: Academic university hospital.

Participants: Patients (60-70 years old) who underwent CABG and received either dexmedetomidine or clonidine infusion postoperatively.

Interventions: Patients were randomly allocated to dexmedetomidine or clonidine groups. In the dexmedetomidine group, patients received an initial infusion of 0.7-1.2 μg/kg/h; sedation and analgesia were evaluated after 45-60 min. If the Richmond assessment sedation score (RASS) increased from +1 to +4, the infusion rate was increased by 0.1-0.2 μg/kg/h every 30 min, up to 1-1.4 μg/kg body-weight/h. Dexmedetomidine infusion was not discontinued pre-extubation; thereafter, infusion was reduced by 0.1 μg/kg/h until 0.2 μg/kg/h. The maximum infusion duration was 72 h. In the clonidine group, patients received an initial infusion of 0.5 μg/kg, followed by 1-2 μg/kg/h, if the RASS changed from +1 to +4. This was continued throughout mechanical ventilation.

Measurements: Patients were followed up to 5 days post-surgery. Delirium incidence, extubation time, lengths of intensive care unit (ICU) and hospital stay, need for inotropic support or vasopressors, mean arterial blood pressure and heart rate, hospital mortality rate, total postoperative morphine dose, number of patients receiving haloperidol, and adverse events were recorded.

Main results: Two-hundred-and-eighty-six patients (dexmedetomidine, 144; clonidine, 142) were studied. Dexmedetomidine was associated with lower risk and duration of delirium, shorter mechanical ventilation duration and ICU stay, lower mortality rate, and lower morphine consumption than the clonidine group. Dexmedetomidine significantly decreased heart rates after ICU admission.

Conclusions: Postoperative infusion of dexmedetomidine provides a feasible option for postoperative control of delirium after CABG in adult patients.

Purpose: This study aimed to investigate incidence, risk factors, and outcomes for sepsis-associated delirium (SAD) in mechanically ventilated patients.

Materials and methods: We performed a retrospective post-hoc analysis of the DExmedetomidine for Sepsis in Intensive care unit Randomized Evaluation (DESIRE) trial. Outcomes included 28-day mortality, ventilator-free days, length of ICU stay, self-extubation, and re-intubation. Multivariable analysis was performed to identify variables independently associated with SAD.

Results: We retrospectively divided the patients into two groups: delirium group (n = 89) and non-delirium group (n = 98). There were no significant differences between the groups in 28-day mortality, self-extubation, and re-intubation. The number of ventilator-free days was significantly less in the delirium vs. non-delirium group (17 vs. 22 days, p = .006), and the length of ICU stay was significantly longer in the delirium group (10 vs. 5 days, p = .04). Multivariable analyses revealed that emergency surgery, more doses of midazolam, and fentanyl were independent predictors for SAD.

Conclusions: SAD was associated with a less number of ventilator-free days and longer length of ICU stay. Emergency surgery, more doses of midazolam, and fentanyl may be independent risk factors for SAD in mechanically ventilated patients with sepsis.

Objectives: Delirium is a serious medical condition with increased incidence in at-risk surgical populations. We sought to determine if melatonin use reduces the incidence of delirium in individuals undergoing major cardiac surgery.

Design: Randomized double-blind placebo-controlled clinical trial (two arms, 1:1 allocation, parallel design).

Setting: The trial took place in two metropolitan hospitals (public tertiary and private) in Perth, Western Australia.

Participants: We recruited 210 adults aged 50 years or older who were due to undergo coronary artery bypass grafting or valve replacement surgery.

Intervention: Participants were randomly assigned (1:1) to 7 days of treatment with melatonin 3 mg at night or matching placebo, starting 2 days before the surgery.

Measurements: The primary outcome of interest was incident delirium within 7 days of surgery as assessed via daily clinical assessment that included the Confusion Assessment Method. Secondary outcomes of interest included duration and severity of delirium, length of hospital stay, cognitive function, and mood and anxiety symptoms at discharge and 3 months after the surgery.

Results: The groups were well balanced for demographic and clinical parameters. Forty-two participants developed delirium, but it was evenly distributed between the groups (melatonin 21/98, 21.4%; placebo 21/104, 20.2%; adjusted odds ratio [OR] = .78; 95% confidence interval [CI] = .35-1.75). The median duration of delirium was 3 (interquartile range [IQR] = 2-4) and 2 (IQR = 1-3) days for people treated with melatonin and placebo, respectively (z = -1.03; P = .304). A similar proportion of participants experienced severe episodes of delirium in each group (melatonin 9/21, 42.9% vs placebo 6/21, 28.6%; χ² = .93; P = .334; adjusted OR = 1.98; 95% CI = .40-9.78). The groups did not differ in terms of length of stay, mood, anxiety, and cognitive performance.

Conclusion: The findings of this randomized double-blind placebo-controlled trial do not support the prophylactic use of melatonin to prevent delirium after major cardiac surgery. J Am Geriatr Soc 68:112-119, 2019.

Objective: The aim of this study was to examine the effectiveness of ramelteon and suvorexant for delirium prevention in real-world practice. It explored whether ramelteon and/or suvorexant would affect delirium prevention among both patients at risk for but without delirium (patients at risk) and those with delirium the night before a consultation.

Methods: This multicenter, prospective, observational study was conducted by trained psychiatrists at consultation-liaison psychiatric services from October 1, 2017, to October 7, 2018. Patients who were aged 65 years or older and hospitalized because of acute diseases or elective surgery, had risk factors for delirium, and had insomnia or delirium on the night before the consultation were prescribed ramelteon and/or suvorexant. The decision to take medication was left to the discretion of each patient. The primary outcome was incidence of delirium based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, during the first 7 days.

Results: Among 526 patients at risk, those taking ramelteon and/or suvorexant developed delirium significantly less frequently than those who did not, after control for the effects of risk factors on the estimate of an independent association between the effects of ramelteon and/or suvorexant and the outcome of developing delirium (15.7% vs 24.0%; odds ratio [OR] = 0.48;, 95% CI, 0.29-0.80; P = .005). Similar results were found among 422 patients with delirium (39.9% vs 66.3%; OR = 0.36; 95% CI, 0.22-0.59; P < .0001).

Conclusions: Ramelteon and suvorexant appear to be effective for delirium prevention in real-world practice.

Background: Dexmedetomidine provides smooth and hemodynamically stable emergence at the expense of hypotension, delayed recovery, and sedation. We investigated the optimal dose of dexmedetomidine for prevention of cough, agitation, hypertension, tachycardia, and shivering, with minimal side effects.

Methods: In this prospective, randomized, double-blind trial, 216 adult patients were randomly assigned to dexmedetomidine 1 µg/kg (D 1), 0.5 µg/kg (D 0.5), 0.25 µg/kg (D 0.25), or control (C). During emergence, cough, agitation, hemodynamic parameters, shivering, time to extubation, and sedation scores were recorded.

Results: A total of 190 patients were analyzed. The respective incidences for the groups D 1, D 0.5, and D 0.25 versus group C were 48%, 64%, and 64% vs 84% for cough-corrected P < .003 between groups D 1 and C; 33%, 34%, and 33% vs 72% for agitation-corrected P < .003 between group C and each of the study groups; and 4%, 2%, and 7% vs 22% for shivering-corrected P = .03 and corrected P = .009 between groups D 1 and D 0.5 versus group C, respectively. The percent increase from baseline blood pressure on extubation for the 3 treatment groups was significantly lower than group C. Percent increase in heart rate was lower than control in groups D 1 and D 0.5 but not in group D 0.25. Time to extubation and sedation scores were comparable. However, more hypotension was recorded during the emergence phase in the 3 treatment groups versus group C.

Conclusions: D 1 at the end of surgery provides the best quality of emergence from general anesthesia including the control of cough, agitation, hypertension, tachycardia, and shivering. D 0.5 also controls emergence phenomena but is less effective in controlling cough. The 3 doses do not delay extubation. However, they cause dose-dependent hypotension.

Objectives: To assess the efficacy of ramelteon in preventing delirium, an acute neuropsychiatric condition associated with increased morbidity and mortality, in the perioperative, ICU setting.

Design: Parallel-arm, randomized, double-blinded, placebo-controlled trial.

Setting: Academic medical center in La Jolla, California.

Patients: Patients greater than or equal to 18 years undergoing elective pulmonary thromboendarterectomy.

Interventions: Ramelteon 8 mg or matching placebo starting the night prior to surgery and for a maximum of six nights while in the ICU.

Measurements and main results: Incident delirium was measured twice daily using the Confusion Assessment Method-ICU. The safety outcome was coma-free days assessed by the Richmond Agitation-Sedation Scale. One-hundred twenty participants were enrolled and analysis completed in 117. Delirium occurred in 22 of 58 patients allocated to placebo versus 19 of 59 allocated to ramelteon (relative risk, 0.8; 95% CI, 0.5-1.4; p = 0.516). Delirium duration, as assessed by the number of delirium-free days was also similar in both groups (placebo median 2 d [interquartile range, 2-3 d] vs ramelteon 3 d [2-5 d]; p = 0.181). Coma-free days was also similar between groups (placebo median 2 d [interquartile range, 1-3 d] vs ramelteon 3 d [2-4 d]; p = 0.210). We found no difference in ICU length of stay (median 4 d [interquartile range, 3-5 d] vs 4 d [3-6 d]; p = 0.349), or in-hospital mortality (four vs three deaths; relative risk ratio, 0.7; 95% CI, 0.2-3.2; p = 0.717), all placebo versus ramelteon, respectively.

Conclusions: Ramelteon 8 mg did not prevent postoperative delirium in patients admitted for elective cardiac surgery.

Purpose: The aim of the study is to compare the free hexafluoro-isopropanol (HFIP) concentration in adults' blood and the incidence of emergence agitation (EA) after inhaled different concentrations of sevoflurane.

Methods: Sixty adult patients planning to undergo laparoscopic gastrointestinal surgery were randomly assigned to 3 groups. Each group received sevoflurane as the volatile anesthetic at different concentrations: 0.5 minimum alveolar concentration (MAC), 1.0 MAC, and 1.5 MAC. The use of sevoflurane was continued until the end of surgery. Venous blood samples were obtained at 30, 60, 120, and 180 minutes after starting the use of sevoflurane and subsequently at 60, 180, and 300 minutes after discontinuation of volatile anesthetic administration. Blood concentrations of sevoflurane and free HFIP were determined using gas chromatography. The recovery time and the incidence of EA at different time points were evaluated among the 3 groups.

Findings: Changes in the blood concentrations of sevoflurane and free HFIP during and after the use of sevoflurane were similar in all 3 groups. The peak blood concentration of free HFIP occurred 60 minutes after onset of sevoflurane anesthesia in all 3 groups (P < 0.05). The lowest level of free HFIP and the longest recovery time were found in the 1.5-MAC group (P < 0.05). No significant difference was found in the incidence of EA or moderate pain among the 3 groups during recovery.

Implications: The generation of HFIP would be inhibited when the inhaled sevoflurane concentration increased to 1.5 MAC. However, the incidence of EA during recovery had nothing to do with the inhaled different sevoflurane concentrations (within 1.5 MAC) in adults. ChicCTR.org identifier: ChiCTR-IPD-17011558.