Characterizing the Heart Rate Effects From Administration of Sugammadex to Reverse Neuromuscular Blockade: An Observational Study in Patients.

BACKGROUND: Reversal of neuromuscular blockade (NMB) with sugammadex can cause marked bradycardia and asystole. Administration of sugammadex typically occurs in a dynamic period when anesthetic adjuvants and gas concentrations are being titrated to achieve emergence. This evaluation examined the heart rate (HR) responses to sugammadex to reverse moderate to deep NMB during a steady-state period and sought mechanisms for HR changes. METHODS: Patients with normal sinus rhythm, who were undergoing elective surgery that included rocuronium for NMB, were evaluated. After surgery, while at steady-state surgical depth anesthesia with sevoflurane and mechanical ventilation, patients received either placebo or 2 or 4 mg/kg of sugammadex to reverse moderate to deep NMB. Study personnel involved in data analysis were blinded to treatment. Continuous electrocardiogram (ECG) was recorded from the 5 minutes before and 5 minutes after sugammadex/placebo administration. R-R intervals were converted to HR and averaged in 1-minute increments. The maximum prolongation of an R-R interval after sugammadex was converted to an instantaneous HR. RESULTS: A total of 63 patients were evaluated: 8 received placebo, and 38 and 17 received 2 and 4 mg/kg sugammadex. Age, body mass index, and patient factors were similar in groups. Placebo did not elicit HR changes, whereas sugammadex caused maximum instantaneous HR slowing (calculated from the longest R-R interval), ranging from 2 to 19 beats/min. There were 7 patients with maximum HR slowing >10 beats/min. The average HR change and 95% confidence interval (CI) during the 5 minutes after 2 mg/kg sugammadex were 3.1 (CI, 2.3-4.1) beats/min, and this was not different from the 4 mg/kg sugammadex group (4.1 beats/min [CI, 2.5-5.6]). HR variability derived from the standard deviation of consecutive R-R intervals increased after sugammadex. CONCLUSIONS: Sugammadex to reverse moderate and deep NMB resulted in a fast onset and variable magnitude of HR slowing in patients. A difference in HR slowing as a function of dose did not achieve statistical significance. The observational nature of the investigation prevented a full understanding of the mechanism(s) of the HR slowing.

Remote ischemic preconditioning prevents deterioration of short-term postoperative cognitive function after cardiac surgery using cardiopulmonary bypass: results of a pilot investigation.

OBJECTIVE: Remote ischemic preconditioning (RIPC) exerts neuroprotective effects in models of cerebral ischemia-reperfusion injury. The authors tested the hypothesis that RIPC decreases the incidence of postoperative delirium and prevents deterioration of short-term postoperative cognitive function in isoflurane-fentanyl-anesthetized patients undergoing cardiac surgery using cardiopulmonary bypass (CPB). DESIGN: Randomized, blinded, single-center pilot investigation. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: Thirty age- and education-matched men≥55 years of age undergoing elective coronary artery or valve surgery using CPB. Fifteen nonsurgical patients also were enrolled. INTERVENTIONS: RIPC was produced after induction of anesthesia using 4 cycles of brief (5 minutes) upper extremity ischemia (tourniquet inflation to 200 mmHg) interspersed with 5-minute periods of reperfusion (tourniquet deflation). MEASUREMENTS AND MAIN RESULTS: The Intensive Care Delirium Screening Checklist was used to assess delirium before and each day after surgery for as many as 5 consecutive days. Recent verbal and nonverbal memory and executive functions were assessed before and 1 week after surgery using a standard neuropsychometric test battery or at 1-week intervals in nonsurgical controls. The Geriatric Depression and the Hachinski Ischemia scales were used to identify the presence of clinical depression and vascular dementia, respectively. No differences in delirium scores were observed between RIPC and control groups (p=0.54). Baseline neurocognitive scores were similar in patients with versus without RIPC in all 3 cognitive domains. Significant declines in performance on 2 nonverbal memory tests (figure reconstruction and delayed figure reproduction; p=0.001 and p=0.003, respectively) and 1 verbal memory test (delayed story recall; p=0.0004) were observed 1 week after surgery in patients who were not treated with RIPC. There were no changes in performance of measures of executive function in this group. In contrast, performance on all cognitive tests was unchanged after compared with before surgery in patients receiving RIPC. At least a 1-standard deviation decline from baseline in cognitive performance was detected in figure reconstruction, delayed figure reproduction, immediate story recall, and delayed story recall in patients who were not exposed to RIPC. The incidence of at least a 1-standard deviation decline in neuropsychometric tests was observed in significantly fewer (1 v 9; p<0.0001) patients with versus without RIPC treatment based on composite Z-scores. Overall cognitive performance after surgery was better in patients treated with versus without RIPC (p=0.002). Clinical depression and vascular dementia were not detected in either group. CONCLUSION: The results of this pilot investigation indicated that RIPC prevented deterioration of short-term postoperative cognitive function but were unable to detect any difference in delirium in isoflurane-fentanyl-anesthetized patients undergoing cardiac surgery using CPB.

Cardiopulmonary bypass transiently inhibits intraventricular vortex ring formation in patients undergoing coronary artery bypass graft surgery.

OBJECTIVE: Transmitral blood flow during early left ventricular (LV) filling produces an intraventricular rotational body of fluid known as a "vortex ring" that enhances the hydraulic efficiency of early LV filling. The authors tested the hypothesis that exposure to cardiopulmonary bypass (CPB) attenuates intraventricular vortex formation time (VFT) in patients with normal preoperative LV systolic and diastolic function undergoing coronary artery bypass graft (CABG) surgery. DESIGN: A prospective, observational study. PARTICIPANTS: Ten men (65 ± 4 years, 91 ± 11 kg, and 175 ± 8 cm) with a normal preoperative LV ejection fraction (58% ± 6%) scheduled for elective CABG surgery were studied after institutional review board approval. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Anesthesia was induced with etomidate, fentanyl, and rocuronium and maintained with isoflurane. Myocardial protection during CPB consisted of antegrade and retrograde cold blood cardioplegia administered at 15-minute intervals, systemic and topical hypothermia, and warm continuous antegrade cardioplegia before aortic cross-clamp removal. The peak early LV filling and atrial systole blood flow velocities (E and A, respectively) and corresponding velocity-time integrals (VTI-E and VTI-A, respectively) were obtained with pulse-wave Doppler echocardiography and used to determine E/A and atrial filling fraction (ß, VTI-A/[VTI-E + VTI-A]), respectively. Mitral valve diameter (D) was calculated as the average of minor and major axis lengths obtained in the midesophageal bicommissural and long-axis transesophageal echocardiographic imaging planes, respectively. VFT was calculated 30 minutes before and 15, 30, and 60 minutes after CPB as 4 × (1 - ß) × stroke volume (SV)/πD(3), where SV is the stroke volume measured using thermodilution. All patients separated from CPB in sinus rhythm without pacing or vasoactive drug support. Systemic and pulmonary hemodynamics were similar before compared with all times after CPB. CPB significantly (p < 0.05) reduced VFT (5.3 ± 1.8 to 4.0 ± 1.5 15 minutes after CPB); the recovery of VFT (to 4.7 ± 1.6, p > 0.05 v baseline) was noted 60 minutes after CPB. A reduction in E/A (1.26 ± 0.22 to 0.96 ± 0.27) and an increase in ß (0.33 ± 0.04 to 0.41 ± 0.07) occurred 15 minutes after CPB. E/A and ß also recovered gradually toward control values after CPB (1.25 ± 0.22 and 0.36 ± 0.04, respectively, 60 minutes after CPB; p > 0.05 v. baseline). CONCLUSIONS: The results indicated that CPB transiently attenuate VFT in patients with normal preoperative LV systolic and diastolic function undergoing CABG surgery. These data suggest that CPB adversely affects diastolic transmitral flow efficiency by reducing intraventricular vortex ring formation in vivo.

Metabolic syndrome exacerbates short-term postoperative cognitive dysfunction in patients undergoing cardiac surgery: results of a pilot study.

OBJECTIVE: The authors tested the hypothesis that patients with metabolic syndrome are more likely to develop short-term cognitive dysfunction after cardiac surgery with cardiopulmonary bypass. DESIGN: A prospective study. SETTING: Veterans Affairs medical center. PARTICIPANTS: Fifty-six age- and education-balanced patients undergoing elective cardiac surgery with cardiopulmonary bypass (28 patients with and without metabolic syndrome in two separate groups) and 28 nonsurgical controls were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Recent verbal and nonverbal memory and executive functions were assessed using a psychometric test battery before and 1 week after cardiac surgery or at 1-week intervals in nonsurgical controls. Neurocognitive scores under the baseline condition were at least 1 z score (1 standard deviation) worse in surgical patients with compared without metabolic syndrome in all 3 cognitive areas (nonverbal and verbal recent memory and executive functions). Neurocognitive performance further deteriorated after surgery by at least 1 z score on 3 tests in the verbal memory modality (Immediate and Delayed Story Recall and Delayed Word List Recall). Overall cognitive performance (composite z score) after surgery was significantly (p = 0.03) worse in metabolic syndrome patients compared with those who did not have the disorder. CONCLUSIONS: The results indicate that short-term cognitive functions were more profoundly impaired in patients with metabolic syndrome undergoing cardiac surgery with cardiopulmonary bypass compared with their healthier counterparts.

Elevated postoperative inflammatory biomarkers are associated with short- and medium-term cognitive dysfunction after coronary artery surgery.

PURPOSE: We tested the hypothesis that elevated postoperative interleukin-6 (IL-6) and C-reactive protein (CRP) concentrations are associated with short- and medium-term impairment of cognitive functions in patients after coronary artery surgery using cardiopulmonary bypass. METHODS: Eighty-six age- and education-balanced patients ≥55 years of age undergoing elective coronary artery bypass surgery with cardiopulmonary bypass and 28 nonsurgical controls with coronary artery disease were enrolled. Recent verbal and nonverbal memory and executive functions were assessed before surgery and at 1 week and 3 months after surgery using a cognitive test battery. IL-6 concentrations were measured before surgery and 4 h after cardiopulmonary bypass, and CRP concentrations were measured before surgery and at 24 and 72 h after anesthetic induction. Overall cognitive function between high and low biomarker concentration groups was analyzed by the Wilcoxon rank-sum test. RESULTS: Recent memory was at least 1 standard deviation (SD) impaired at 1 week and 3 months in the high-CRP compared with low-CRP and in the high-IL-6 compared with low-IL-6 concentration groups. Overall cognitive function was significantly (P = 0.04 and P = 0.01, respectively) different between the high- and low-CRP concentration groups (CRP assayed 24 h after anesthetic induction) at both 1 week and 3 months. Overall cognitive function was also significantly (P = 0.04) different between the high and low-IL-6 concentration groups at 1 week after surgery. CONCLUSION: The results suggest that elevated postoperative IL-6 and CRP concentrations are associated with the subsequent development of short- and medium-term impairment of cognitive functions after coronary artery surgery.

Postoperative delirium and short-term cognitive dysfunction occur more frequently in patients undergoing valve surgery with or without coronary artery bypass graft surgery compared with coronary artery bypass graft surgery alone: results of a pilot study.

OBJECTIVE: The authors tested the hypothesis that patients undergoing valve repair or replacement surgery with or without coronary artery bypass graft (CABG) surgery using cardiopulmonary bypass (CPB) had a greater incidence of postoperative delirium and cognitive dysfunction compared with patients undergoing CABG surgery alone. DESIGN: Prospective study. SETTING: Veterans Affairs medical center. PARTICIPANTS: Forty-four age- and education-balanced male patients (≥ 55 years of age) undergoing elective cardiac surgery with CPB (n = 22 valve ± CABG surgery and n = 22 CABG surgery alone) and nonsurgical controls (n = 22) were recruited. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Delirium was assessed with the Intensive Care Delirium Screening Checklist before and for 5 consecutive days after surgery. Recent verbal and nonverbal memory and executive functions were assessed using a psychometric test battery before and 1 week after cardiac surgery or at 1-week intervals in nonsurgical controls. Intensive care unit stay, hospital stay, and 30-day readmission were significantly (p = 0.03, p = 0.01, and p = 0.04, respectively) longer in patients undergoing valve surgery ± CABG surgery versus CABG surgery alone. Postoperative delirium occurred more frequently (p = 0.01) in patients undergoing valve ± CABG surgery versus CABG surgery alone. Overall cognitive performance (composite z score) after surgery also was impaired significantly (p = 0.004) in patients undergoing valve ± CABG surgery compared with CABG surgery alone. The composite z score after surgery decreased by at least 1.5 standard deviations in 11 patients (50%) versus 1 patient (5%) without valve surgery compared with nonsurgical controls (p = 0.001, Fisher's exact test). The presence of delirium predicted a composite z score decrease of 1.2 points (odds ratio = 0.30; 95% confidence interval, 0.13-0.68). CONCLUSIONS: The results indicated that patients undergoing valve surgery with or without CABG surgery have a higher incidence of postoperative delirium and cognitive dysfunction 1 week after surgery compared with those undergoing CABG surgery alone.

History of post-traumatic stress disorder is associated with impaired neuropsychometric performance after coronary artery surgery.

OBJECTIVE: To determine if preoperative history of post-traumatic stress disorder (PTSD) is associated with postoperative cognitive impairment. DESIGN: An observational study. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: Cardiac surgical patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Age- and education-balanced patients (≥55 years of age) undergoing cardiac surgery (n = 30 with a history of PTSD+, n = 56 without a history of PTSD-) and nonsurgical controls (n = 28) were recruited. Recent verbal and nonverbal memory and executive functions were assessed before and 1 week after cardiac surgery or at 1-week intervals in nonsurgical controls. Demographic and medical parameters were similar between groups with the exception of preoperative depression and a history of alcohol dependence. Preoperative depression scores were significantly (p = 0.02) higher in PTSD+ compared with PTSD- groups. Immediate Word List Recall and Delayed Word List Recall under baseline conditions were worse in PTSD+ compared with PTSD- patients. Cognitive performance after surgery decreased by at least 1 standard deviation in 27 PTSD- patients (48%) and in 25 PTSD+ patients (83%) (p = 0.002) versus nonsurgical controls. Multivariate regression analysis (including a history of depression and alcohol dependence) revealed that a history of PTSD was significantly associated with overall (including nonverbal recent memory, verbal recent memory, and executive functions) postoperative cognitive dysfunction (p = 0.005). CONCLUSIONS: The current findings suggest that patients with a history of PTSD undergoing coronary artery surgery using cardiopulmonary bypass may be especially vulnerable to postoperative cognitive impairment.

Preoperative dispositional optimism correlates with a reduced incidence of postoperative delirium and recovery of postoperative cognitive function in cardiac surgical patients.

OBJECTIVE: To determine if preoperative psychosocial factors including dispositional optimism, perceived social support, and perceived stress correlate with the recovery of postoperative cognition. DESIGN: Observational study. SETTING: Veterans Affairs medical center. PARTICIPANTS: Cardiac surgical patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Age- and education-balanced patients (> or =55 years of age) undergoing cardiac surgery (n = 40) and nonsurgical controls (n = 40) were recruited. A psychosocial evaluation for dispositional optimism, perceived social support, perceived stress, and depression was performed before surgery using standardized questionnaires. Delirium was assessed with the Intensive Care Delirium Screening Checklist before and for 5 consecutive days after surgery. Recent verbal and nonverbal memory and executive functions were assessed before and 1 week after cardiac surgery or at 1-week intervals in nonsurgical controls. Preoperative perceived stress significantly (p < 0.01) correlated with preoperative depression scores. Preoperative dispositional optimism significantly (p < 0.05) correlated with preoperative perceived social support. A multiple logistic regression revealed that dispositional optimism significantly (p < 0.02) predicted the absence of postoperative delirium within 5 days of surgery. Patients who showed high levels of dispositional optimism suffered a significantly (p < 0.03) lower incidence of postoperative delirium. Preoperative dispositional optimism also significantly (p < 0.001) correlated with a postoperative cognitive performance determined by composite z scores. A stepwise multiple regression analysis revealed that dispositional optimism significantly (p < 0.05, R(2) = 35%) predicted postoperative cognitive function. CONCLUSIONS: Preoperative dispositional optimism, but not perceived social support, perceived stress, and depression positively correlated with a reduced incidence of postoperative delirium within 5 days and recovery of cognitive performance 1 week after cardiac surgery.

Ketamine attenuates delirium after cardiac surgery with cardiopulmonary bypass.

OBJECTIVE: To determine if ketamine attenuates postoperative delirium concomitant with an anti-inflammatory effect in patients undergoing cardiac surgery using cardiopulmonary bypass. DESIGN: A prospective randomized study. SETTING: A Veterans Affairs medical center. PARTICIPANTS: Cardiac surgical patients. INTERVENTIONS: Patients at least 55 years of age randomly received placebo (0.9% saline, n = 29) or an intravenous bolus of ketamine (0.5 mg/kg intravenously, n = 29) during anesthetic induction in the presence of fentanyl and etomidate. MEASUREMENTS AND MAIN RESULTS: Delirium was assessed by using the Intensive Care Delirium Screening Checklist before and after surgery. Serum C-reactive protein concentrations were determined before and 1 day after surgery. The incidence of postoperative delirium was lower (p = 0.01, Fisher exact test) in patients receiving ketamine (3%) compared with placebo (31%). Postoperative C-reactive protein concentration was also lower (p < 0.05) in the ketamine-treated patients compared with the placebo-treated patients. The odds of developing postoperative delirium were greater for patients receiving placebo compared with ketamine treatment (odds ratio = 12.6; 95% confidence interval, 1.5-107.5; logistic regression). CONCLUSIONS: After cardiac surgery using cardiopulmonary bypass, ketamine attenuates postoperative delirium concomitant with an anti-inflammatory effect.

A history of alcohol dependence increases the incidence and severity of postoperative cognitive dysfunction in cardiac surgical patients.

Postoperative cognitive dysfunction (POCD) commonly occurs after cardiac surgery. We tested the hypothesis that a history of alcohol dependence is associated with an increased incidence and severity of POCD in male patients undergoing cardiac surgery using cardiopulmonary bypass. Recent verbal and nonverbal memory and executive functions were assessed before and one week after surgery in patients with or without a history of alcohol dependence. Cognitive function was significantly reduced after cardiac surgery in patients with versus without a history of alcohol dependence. The results suggest that a history of alcohol dependence increases the incidence and severity of POCD after cardiac surgery.

Treatment of acute postoperative hypertension in cardiac surgery patients: an efficacy study of clevidipine assessing its postoperative antihypertensive effect in cardiac surgery-2 (ESCAPE-2), a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Acute postoperative hypertension is a well-known complication of cardiac surgery and is associated with postoperative morbidity. Clevidipine, an ultrashort-acting, third-generation dihydropyridine calcium channel blocker, exerts vascular-selective, arterial-specific vasodilation to decrease arterial blood pressure without negatively impacting cardiac function. In this double-blind, placebo-controlled trial, we examined the efficacy and safety of clevidipine in treating postoperative hypertension in cardiac surgery patients. METHODS: Two hundred six patients undergoing cardiac surgery were randomized preoperatively. Of these, 110 met postrandomization inclusion criteria for the study [systolic blood pressure (SBP) >or=140 mm Hg within 4 h of admission to a postoperative setting, and clinically assessed as needing SBP reduction by >or=15% from baseline]. Patients received an infusion of either clevidipine (0.4-8.0 microg kg(-1) min(-1)) or 20% lipid emulsion (placebo) for 30 min to a maximum of 1 h unless treatment failure occurred sooner. The primary end point was the incidence of treatment failure, defined as the inability to decrease SBP by >or=15% from baseline, or the discontinuation of study treatment for any reason within the 30-min period after study drug initiation. RESULTS: Clevidipine-treated patients had a significantly lower incidence of treatment failure than placebo patients [8.2% (5 of 61) vs 79.6% (39 of 49), P < 0.0001]. Treatment success was achieved in 91.8% of clevidipine-treated patients. Median time to target SBP with clevidipine was 5.3 min (95% confidence interval, 4-7 min). No clinically significant increase in heart rate from baseline was observed. Adverse event rates were similar for both treatment groups. CONCLUSIONS: Clevidipine is effective and safe in the rapid treatment of acute postoperative hypertension after cardiac surgery.