Enhanced recovery after cardiac surgery protocol reduces perioperative opioid use.

Objective: Enhanced Recovery After Surgery protocols are relatively new in cardiac surgery. Enhanced Recovery After Surgery addresses perioperative analgesia by implementing multimodal pain control regimens that include both opioid and nonopioid components. We investigated the effects of an Enhanced Recovery After Surgery protocol at our institution on postoperative outcomes with particular focus on analgesia. Methods: Single-center retrospective study comparing perioperative opioid use before and after implementation of an Enhanced Recovery After Surgery protocol at our institution. Subjects were divided into 2 cohorts: Enhanced Recovery After Surgery (study group from year 2020) and pre-Enhanced Recovery After Surgery (control group from year 2018). Baseline and perioperative variables including total opioid use from the day of surgery to postoperative day 5 were collected. Opioid use was calculated as morphine milligram equivalents and compared between the 2 cohorts. Results: A total of 466 patients were included: 250 in the Enhanced Recovery After Surgery group and 216 in the pre-Enhanced Recovery After Surgery group. Both groups had similar baseline characteristics, but the Enhanced Recovery After Surgery group had significantly more subjects with intravenous drug use history (P < .0001), endocarditis (P < .0001), and liver disease (P = .007) compared with the pre-Enhanced Recovery After Surgery group. Every day from the day of surgery to postoperative day 5, the Enhanced Recovery After Surgery group had significant reduction (57%) in opioid use compared with the pre-Enhanced Recovery After Surgery group. Total opioid use for the entire length of stay was 259 morphine milligram equivalents in the Enhanced Recovery After Surgery group versus 452 morphine milligram equivalents in the pre-Enhanced Recovery After Surgery group (P < .0001). Subgroup analysis of subjects with intravenous drug use history did not demonstrate a significant reduction in opioid use. Conclusions: Enhanced Recovery After Surgery protocols with an emphasis on multimodal pain management throughout perioperative care are associated with a significant reduction in the postoperative use of opioid analgesics.

Outcomes of Surgical Coronary Revascularization Performed Before Solid Abdominal Organ Transplants.

BACKGROUND: Cardiac risk stratification and coronary angiography are routinely performed as part of kidney and liver transplant candidacy evaluation. There are limited data on the outcomes of surgical coronary revascularization in this patient population. This study investigated outcomes in patients with end- stage renal or hepatic disease who were undergoing coronary artery bypass grafting (CABG) to attain kidney or liver transplant candidacy. METHODS: This study was a retrospective analysis of all patients who underwent isolated CABG at our institution, Indiana University School of Medicine (Indianapolis, IN), between 2010 and 2016. Patients were divided into 2 cohorts: pretransplant (those undergoing surgery to attain renal or hepatic transplant candidacy) and nontransplant (all others). Baseline characteristics and postoperative outcomes were compared between the groups. RESULTS: A total of 1801 patients were included: 28 in the pretransplant group (n = 22, kidney; n = 7, liver) and 1773 in the nontransplant group. Major adverse postoperative outcomes were significantly greater in the pretransplant group compared with the nontransplant group: 30-day mortality (14.3% vs 2.8%; P = .009), neurologic events (17.9% vs 4.8%; P = .011), reintubation (21.4% vs 5.8%; P = .005), and total postoperative ventilation (5.2 hours vs 5.0 hours; P = .0124). The 1- and 5-year mortality in the pretransplant group was 17.9% and 53.6%, respectively. Of the pretransplant cohort, 3 patients (10.7%) underwent organ transplantation (all kidney) at a mean 436 days after CABG. No patients underwent liver transplantation. CONCLUSIONS: Outcomes after CABG in pre-kidney transplant and pre-liver transplant patients are poor. Despite surgical revascularization, most patients do not ultimately undergo organ transplantation. Revascularization strategies and optimal management in this high-risk population warrant further study.

Acute Phencyclidine Alters Neural Oscillations Evoked by Tones in the Auditory Cortex of Rats.

BACKGROUND/AIMS: The onset response to a single tone as measured by electroencephalography (EEG) is diminished in power and synchrony in schizophrenia. Because neural synchrony, particularly at gamma frequencies (30-80 Hz), is hypothesized to be supported by the N-methyl-D-aspartate receptor (NMDAr) system, we tested whether phencyclidine (PCP), an NMDAr antagonist, produced similar deficits to tone stimuli in rats. METHODS: Experiment 1 tested the effect of a PCP dose (1.0, 2.5, and 4.5 mg/kg) on response to single tones on intracranial EEG recorded over the auditory cortex in rats. Experiment 2 evaluated the effect of PCP after acute administration of saline or PCP (5 mg/kg), after continuous subchronic administration of saline or PCP (5 mg/kg/day), and after a week of drug cessation. In both experiments, a time-frequency analysis quantified mean power (MP) and phase locking factor (PLF) between 1 and 80 Hz. Event-related potentials (ERPs) were also measured to tones, and EEG spectral power in the absence of auditory stimuli. RESULTS: Acute PCP increased PLF and MP between 10 and 30 Hz, while decreasing MP and PLF between approximately 50 and 70 Hz. Acute PCP produced a dose-dependent broad-band increase in EEG power that extended into gamma range frequencies. There were no consistent effects of subchronic administration on gamma range activity. Acute PCP increased ERP amplitudes for the P16 and N70 components. CONCLUSIONS: Findings suggest that acute PCP-induced NMDAr hypofunction has differential effects on neural power and synchrony which vary with dose, time course of administration and EEG frequency. EEG synchrony and power appear to be sensitive translational biomarkers for disrupted NMDAr function, which may contribute to the pathophysiology of schizophrenia and other neuropsychiatric disorders.

Negative urgency, mood induction, and alcohol seeking behaviors.

BACKGROUND: Negative urgency, defined as impulsive risk-taking during extreme negative emotional states, is the most important impulsivity-related trait for alcohol-related problems and alcohol dependence. However, how negative urgency imparts risk for alcohol-related problems is not yet well understood. Therefore, the goal of the current study was to examine how negative urgency relates to separable aspects of the emotional experience and alcohol-seeking behaviors. METHODS: A total of 34 (19 women) community-dwelling, alcohol-using adults aged 21-32 (mean age=24.86, SD=3.40, 74.3% Caucasian) completed two counterbalanced intravenous alcohol self-administration sessions: one during a neutral mood condition and one during a negative mood condition. RESULTS: Negative urgency was associated with 1) greater mood change following negative mood induction (F=4.38, df=15, p=0.002, η2=0.87), but was unrelated to changes in craving or cortisol release in response to mood induction; 2) greater alcohol craving prior to and after an alcohol prime (F=3.27, p=0.02, η2=0.86), but only in the negative and not the neutral mood condition; and 3) higher peak BrAC (F=2.13, df=42, p=0.02, η2=0.48), continuing to increase intoxication level over a longer period (F=3.77, df=42, p<0.001, η2=0.62), and more alcohol seeking (F=21.73, df=22, p<0.001, η2=0.94) throughout the negative session. Negative urgency was associated with overall lower cortisol release. CONCLUSIONS: These results highlight the importance of assessing behavioral indicators of negative urgency under mood condition, and suggest that negative urgency may amplify alcohol self-administration through increased negative emotional reactivity to mood events and increased alcohol craving after initial alcohol exposure, leading to maintenance of alcohol related behavior.

Gender-Specific Effects of Mood on Alcohol-Seeking Behaviors: Preliminary Findings Using Intravenous Alcohol Self-Administration.

BACKGROUND: Although negative mood has long been implicated in differences in alcohol seeking by men and women, little research has used precise, well-controlled laboratory experiments to examine how negative mood affects alcohol-seeking behaviors. METHODS: A total of 34 (19 women) community-dwelling, alcohol-using adults aged 21 to 32 (mean age = 24.86, SD = 3.40, 74.3% Caucasian; Alcohol Use Disorders Identification Test [AUDIT] = 10.1, SD = 3.4) completed 2 counterbalanced intravenous alcohol self-administration sessions: one under negative mood and one under neutral mood. Fourteen individuals (9 women; mean age = 25.00, SD = 2.77) participated in an alcohol "liking" experiment (i.e., free access [FA] drinking) and 20 individuals (10 women; mean age = 24.77, SD = 3.73) participated in an alcohol "wanting" experiment, in which gaining access to alcohol required progressively effortful work. There was no significant difference between men and women on the AUDIT, t(32) = -0.38, p = 0.71. RESULTS: Priming with negative mood induction caused a significant decrease in self-reported mood (mean change = -1.85, t(32) = -6.81, p < 0.001), as intended. In FA, negative mood was associated with a significantly increased peak breath alcohol concentration (BrAC; F = 9.41, p = 0.01), with a trend toward a greater effect in men than in women (F = 2.67, p = 0.13). Negative mood also had a significant effect on peak BrAC achieved in the progressive work paradigm (F = 5.28, p = 0.04), with a significantly stronger effect in men (F = 5.35, p = 0.03) than women; men also trended toward more consistent work for alcohol across both neutral and negative sessions. CONCLUSIONS: These preliminary findings demonstrate a gender-specific response on how mood affects alcohol seeking and suggest gender-specific interventions to prevent mood-based alcohol consumption.

Phencyclidine Disrupts the Auditory Steady State Response in Rats.

The Auditory Steady-State Response (ASSR) in the electroencephalogram (EEG) is usually reduced in schizophrenia (SZ), particularly to 40 Hz stimulation. The gamma frequency ASSR deficit has been attributed to N-methyl-D-aspartate receptor (NMDAR) hypofunction. We tested whether the NMDAR antagonist, phencyclidine (PCP), produced similar ASSR deficits in rats. EEG was recorded from awake rats via intracranial electrodes overlaying the auditory cortex and at the vertex of the skull. ASSRs to click trains were recorded at 10, 20, 30, 40, 50, and 55 Hz and measured by ASSR Mean Power (MP) and Phase Locking Factor (PLF). In Experiment 1, the effect of different subcutaneous doses of PCP (1.0, 2.5 and 4.0 mg/kg) on the ASSR in 12 rats was assessed. In Experiment 2, ASSRs were compared in PCP treated rats and control rats at baseline, after acute injection (5 mg/kg), following two weeks of subchronic, continuous administration (5 mg/kg/day), and one week after drug cessation. Acute administration of PCP increased PLF and MP at frequencies of stimulation below 50 Hz, and decreased responses at higher frequencies at the auditory cortex site. Acute administration had a less pronounced effect at the vertex site, with a reduction of either PLF or MP observed at frequencies above 20 Hz. Acute effects increased in magnitude with higher doses of PCP. Consistent effects were not observed after subchronic PCP administration. These data indicate that acute administration of PCP, a NMDAR antagonist, produces an increase in ASSR synchrony and power at low frequencies of stimulation and a reduction of high frequency (> 40 Hz) ASSR activity in rats. Subchronic, continuous administration of PCP, on the other hand, has little impact on ASSRs. Thus, while ASSRs are highly sensitive to NMDAR antagonists, their translational utility as a cross-species biomarker for NMDAR hypofunction in SZ and other disorders may be dependent on dose and schedule.