Andra E. Duncan

Role of Intraoperative and Postoperative Blood Glucose Concentrations in Predicting Outcomes after Cardiac Surgery

Background:Severe hyperglycemia is associated with adverse outcomes after cardiac surgery. Whether intraoperative and postoperative glucose concentrations equally impact outcomes is unknown. The objective of this investigation was to compare the ability of perioperative glucose concentrations and glycemic variability to predict adverse outcomes. Risk associated with decreasing increments of glucose concentrations, hypoglycemia, and diabetic status was also examined. Methods:This retrospective analysis of prospectively collected data included 4,302 patients who underwent cardiac surgery between October 3, 2005 and May 31, 2007 at the Cleveland Clinic. Time-weighted mean intraoperative (GlcOR) and postoperative (GlcICU) glucose concentrations were calculated. Patients were categorized as follows: Glc more than 200, 171–200, 141–170, and less than or equal to 140 mg/dl. Coefficient of variation was used to calculate glycemic variability. Logistic regression model with backward selection assessed the relationship between glucose concentrations, variability, and adverse outcomes while adjusting for potential confounders. Another model assessed the predictability of GlcOR and GlcICU on adverse outcomes. Results:Both GlcOR and GlcICU predicted risk for mortality and morbidity. Increased postoperative glycemic variability was associated with increased risk for adverse outcomes. Severe hyperglycemia (GlcOR and GlcICU > 200 mg/dl) was associated with worse outcomes; however, decreasing increments of GlcOR did not consistently reduce risk. GlcOR less than or equal to 140 mg/dl was not associated with improved outcomes compared with severe hyperglycemia, despite infrequent hypoglycemia. Diabetic status did not influence the effects of hyperglycemia. Conclusion:Perioperative glucose concentrations and glycemic variability are important in predicting outcomes after cardiac surgery. Incremental decreases of intraoperative glucose concentrations did not consistently reduce risk. Despite rare hypoglycemia, intraoperative glucose concentrations closest to normoglycemia were associated with worse outcomes.

Effects of remote ischemic preconditioning in high-risk patients undergoing cardiac surgery (Remote IMPACT): a randomized controlled trial

Background: Remote ischemic preconditioning is a simple therapy that may reduce cardiac and kidney injury. We undertook a randomized controlled trial to evaluate the effect of this therapy on markers of heart and kidney injury after cardiac surgery. Methods: Patients at high risk of death within 30 days after cardiac surgery were randomly assigned to undergo remote ischemic preconditioning or a sham procedure after induction of anesthesia. The preconditioning therapy was three 5-minute cycles of thigh ischemia, with 5 minutes of reperfusion between cycles. The sham procedure was identical except that ischemia was not induced. The primary outcome was peak creatine kinase–myocardial band (CK-MB) within 24 hours after surgery (expressed as multiples of the upper limit of normal, with log transformation). The secondary outcome was change in creatinine level within 4 days after surgery (expressed as log-transformed micromoles per litre). Patient-important outcomes were assessed up to 6 months after randomization. Results: We randomly assigned 128 patients to remote ischemic preconditioning and 130 to the sham therapy. There were no significant differences in postoperative CK-MB (absolute mean difference 0.15, 95% confidence interval [CI] −0.07 to 0.36) or creatinine (absolute mean difference 0.06, 95% CI −0.10 to 0.23). Other outcomes did not differ significantly for remote ischemic preconditioning relative to the sham therapy: for myocardial infarction, relative risk (RR) 1.35 (95% CI 0.85 to 2.17); for acute kidney injury, RR 1.10 (95% CI 0.68 to 1.78); for stroke, RR 1.02 (95% CI 0.34 to 3.07); and for death, RR 1.47 (95% CI 0.65 to 3.31). Interpretation: Remote ischemic precnditioning did not reduce myocardial or kidney injury during cardiac surgery. This type of therapy is unlikely to substantially improve patient-important outcomes in cardiac surgery. Trial registration: ClinicalTrials.gov, no. NCT01071265.

Intraoperative Tight Glucose Control Using Hyperinsulinemic Normoglycemia Increases Delirium after Cardiac Surgery

Background:Postoperative delirium is common in patients recovering from cardiac surgery. Tight glucose control has been shown to reduce mortality and morbidity. Therefore, the authors sought to determine the effect of tight intraoperative glucose control using a hyperinsulinemic–normoglycemic clamp approach on postoperative delirium in patients undergoing cardiac surgery. Methods:The authors enrolled 198 adult patients having cardiac surgery in this randomized, double-blind, single-center trial. Patients were randomly assigned to either tight intraoperative glucose control with a hyperinsulinemic–normoglycemic clamp (target blood glucose, 80 to 110 mg/dl) or standard therapy (conventional insulin administration with blood glucose target, <150 mg/dl). Delirium was assessed using a comprehensive delirium battery. The authors considered patients to have experienced postoperative delirium when Confusion Assessment Method testing was positive at any assessment. A positive Confusion Assessment Method was defined by the presence of features 1 (acute onset and fluctuating course) and 2 (inattention) and either 3 (disorganized thinking) or 4 (altered consciousness). Results:Patients randomized to tight glucose control were more likely to be diagnosed as being delirious than those assigned to routine glucose control (26 of 93 vs. 15 of 105; relative risk, 1.89; 95% CI, 1.06 to 3.37; P = 0.03), after adjusting for preoperative usage of calcium channel blocker and American Society of Anesthesiologist physical status. Delirium severity, among patients with delirium, was comparable with each glucose management strategy. Conclusion:Intraoperative hyperinsulinemic–normoglycemia augments the risk of delirium after cardiac surgery, but not its severity.

Perioperative assessment of myocardial deformation.

Evaluation of left ventricular performance improves risk assessment and guides anesthetic decisions. However, the most common echocardiographic measure of myocardial function, the left ventricular ejection fraction (LVEF), has important limitations. LVEF is limited by subjective interpretation that reduces accuracy and reproducibility, and LVEF assesses global function without characterizing regional myocardial abnormalities. An alternative objective echocardiographic measure of myocardial function is thus needed. Myocardial deformation analysis, which performs quantitative assessment of global and regional myocardial function, may be useful for perioperative care of surgical patients. Myocardial deformation analysis evaluates left ventricular mechanics by quantifying strain and strain rate. Strain describes percent change in myocardial length in the longitudinal (from base to apex) and circumferential (encircling the short-axis of the ventricle) direction and change in thickness in the radial direction. Segmental strain describes regional myocardial function. Strain is a negative number when the ventricle shortens longitudinally or circumferentially and is positive with radial thickening. Reference values for normal longitudinal strain from a recent meta-analysis by using transthoracic echocardiography are (mean ± SD) −19.7% ± 0.4%, while radial and circumferential strain are 47.3% ± 1.9% and −23.3% ± 0.7%, respectively. The speed of myocardial deformation is also important and is characterized by strain rate. Longitudinal systolic strain rate in healthy subjects averages −1.10 ± 0.16 s−1. Assessment of myocardial deformation requires consideration of both strain (change in deformation), which correlates with LVEF, and strain rate (speed of deformation), which correlates with rate of rise of left ventricular pressure (dP/dt). Myocardial deformation analysis also evaluates ventricular relaxation, twist, and untwist, providing new and noninvasive methods to assess components of myocardial systolic and diastolic function. Myocardial deformation analysis is based on either Doppler or a non-Doppler technique, called speckle-tracking echocardiography. Myocardial deformation analysis provides quantitative measures of global and regional myocardial function for use in the perioperative care of the surgical patient. For example, coronary graft occlusion after coronary artery bypass grafting is detected by an acute reduction in strain in the affected coronary artery territory. In addition, assessment of left ventricular mechanics detects underlying myocardial pathology before abnormalities become apparent on conventional echocardiography. Certainly, patients with aortic regurgitation demonstrate reduced longitudinal strain before reduction in LVEF occurs, which allows detection of subclinical left ventricular dysfunction and predicts increased risk for heart failure and impaired myocardial function after surgical repair. In this review, we describe the principles, techniques, and clinical application of myocardial deformation analysis.

Increased intraoperative fluid administration is associated with severe primary graft dysfunction after lung transplantation

BACKGROUND:Severe primary graft dysfunction (PGD) is a major cause of early morbidity and mortality in patients after lung transplantation. The etiology and pathophysiology of PGD is not fully characterized and whether intraoperative fluid administration increases the risk for PGD remains unclear from previous studies. Therefore, we tested the hypothesis that increased total intraoperative fluid volume during lung transplantation is associated with the development of grade-3 PGD. METHODS:This retrospective cohort analysis included patients who had lung transplantation at the Cleveland Clinic between January 2009 and June 2013. We used multivariable logistic regression with adjustment for donor, recipient, and perioperative confounding factors to examine the association between total intraoperative fluid administration and development of grade-3 PGD in the initial 72 postoperative hours. Secondary outcomes included time to initial extubation and intensive care unit length of stay. RESULTS:Grade-3 PGD occurred in 123 of 494 patients (25%) who had lung transplantation. Patients with grade-3 PGD received a larger volume of intraoperative fluid (median 5.0 [3.8, 7.5] L) than those without grade-3 PGD (3.9 [2.8, 5.2] L). Each intraoperative liter of fluid increased the odds of grade-3 PGD by approximately 22% (adjusted odds ratio, 1.22; 95% confidence interval [CI], 1.12–1.34; P <0.001). The volume of transfused red blood cell concentrate was associated with grade-3 PGD (1.1 [0.0, 1.8] L for PGD-3 vs 0.4 [0.0, 1.1 for nongrade-3 PGD] L; adjusted odds ratio, 1.7; 95% CI, 1.08–2.7; P = 0.002). Increased fluid administration was associated with longer intensive care unit stay (adjusted hazard ratio, 0.92; 97.5% CI, 0.88–0.97; P < 0.001) but not with time to initial tracheal extubation (hazard ratio, 0.97; 97.5% CI, 0.93–1.02; P = 0.17). CONCLUSIONS:Increased intraoperative fluid volume is associated with the most severe form of PGD after lung transplant surgery. Limiting fluid administration may reduce the risk for development of grade-3 PGD and thus improve early postoperative morbidity and mortality after lung transplantation.

Early left and right ventricular response to aortic valve replacement

BACKGROUND: The immediate effect of aortic valve replacement (AVR) for aortic stenosis on perioperative myocardial function is unclear. Left ventricular (LV) function may be impaired by cardioplegia-induced myocardial arrest and ischemia-reperfusion injury, especially in patients with LV hypertrophy. Alternatively, LV function may improve when afterload is reduced after AVR. The right ventricle (RV), however, experiences cardioplegic arrest without benefiting from improved loading conditions. Which of these effects on myocardial function dominate in patients undergoing AVR for aortic stenosis has not been thoroughly explored. Our primary objective is thus to characterize the effect of intraoperative events on LV function during AVR using echocardiographic measures of myocardial deformation. Second, we evaluated RV function. METHODS: In this supplementary analysis of 100 patients enrolled in a clinical trial (NCT01187329), 97 patients underwent AVR for aortic stenosis. Of these patients, 95 had a standardized intraoperative transesophageal echocardiographic examination of systolic and diastolic function performed before surgical incision and repeated after chest closure. Echocardiographic images were analyzed off-line for global longitudinal myocardial strain and strain rate using 2D speckle-tracking echocardiography. Myocardial deformation assessed at the beginning of surgery was compared with the end of surgery using paired t tests corrected for multiple comparisons. RESULTS: LV volumes and arterial blood pressure decreased, and heart rate increased at the end of surgery. Echocardiographic images were acceptable for analysis in 72 patients for LV strain, 67 for LV strain rate, and 54 for RV strain and strain rate. In 72 patients with LV strain images, 9 patients required epinephrine, 22 required norepinephrine, and 2 required both at the end of surgery. LV strain did not change at the end of surgery compared with the beginning of surgery (difference: 0.7 [97.6% confidence interval, −0.2 to 1.5]%; P = 0.07), whereas LV systolic strain rate improved (became more negative) (−0.3 [−0.4 to −0.2] s−1; P < 0.001). In contrast, RV systolic strain worsened (became less negative) at the end of surgery (difference: 4.6 [3.1 to 6.0]%; P < 0.001) although RV systolic strain rate was unchanged (0.0 [97.6% confidence interval, −0.1 to 0.1]; P = 0.83). CONCLUSIONS: LV function improved after replacement of a stenotic aortic valve demonstrated by improved longitudinal strain rate. In contrast, RV function, assessed by longitudinal strain, was reduced.

Hyperinsulinemic Normoglycemia Does Not Meaningfully Improve Myocardial Performance during Cardiac Surgery: A Randomized Trial.

Background:Glucose–insulin–potassium (GIK) administration during cardiac surgery inconsistently improves myocardial function, perhaps because hyperglycemia negates the beneficial effects of GIK. The hyperinsulinemic normoglycemic clamp (HNC) technique may better enhance the myocardial benefits of GIK. The authors extended previous GIK investigations by (1) targeting normoglycemia while administering a GIK infusion (HNC); (2) using improved echocardiographic measures of myocardial deformation, specifically myocardial longitudinal strain and strain rate; and (3) assessing the activation of glucose metabolic pathways. Methods:A total of 100 patients having aortic valve replacement for aortic stenosis were randomly assigned to HNC (high-dose insulin with concomitant glucose infusion titrated to normoglycemia) versus standard therapy (insulin treatment if glucose >150 mg/dl). The primary outcomes were left ventricular longitudinal strain and strain rate, assessed using speckle-tracking echocardiography. Right atrial tissue was analyzed for activation of glycolysis/pyruvate oxidation and alternative metabolic pathways. Results:Time-weighted mean glucose concentrations were lower with HNC (127 ± 19 mg/dl) than standard care (177 ± 41 mg/dl; P < 0.001). Echocardiographic data were adequate in 72 patients for strain analysis and 67 patients for strain rate analysis. HNC did not improve myocardial strain, with an HNC minus standard therapy difference of −1.2% (97.5% CI, −2.9 to 0.5%; P = 0.11). Strain rate was significantly better, but by a clinically unimportant amount: −0.16 s−1 (−0.30 to −0.03 s−1; P = 0.007). There was no evidence of increased glycolytic, pyruvate oxidation, or hexosamine biosynthetic pathway activation in right atrial samples (HNC, n = 20; standard therapy, 22). Conclusion:Administration of glucose and insulin while targeting normoglycemia during aortic valve replacement did not meaningfully improve myocardial function.

Brachial arterial pressure monitoring during cardiac surgery rarely causes complications

Background: Brachial arterial catheters better estimate aortic pressure than radial arterial catheters but are used infrequently because complications in a major artery without collateral flow are potentially serious. However, the extent to which brachial artery cannulation promotes complications remains unknown. The authors thus evaluated a large cohort of cardiac surgical patients to estimate the incidence of related serious complications. Methods: The institutional Society of Thoracic Surgeons Adult Cardiac Surgery Database and Perioperative Health Documentation System Registry of the Cleveland Clinic were used to identify patients who had brachial artery cannulation between 2007 and 2015. Complications within 6 months after surgery were identified by International Classification of Diseases, Ninth Revision diagnostic and procedural codes, Current Procedural Terminology procedure codes, and Society of Thoracic Surgeons variables. The authors reviewed electronic medical records to confirm that putative complications were related plausibly to brachial arterial catheterization. Complications were categorized as (1) vascular, (2) peripheral nerve injury, or (3) infection. The authors evaluated associations between brachial arterial complications and patient comorbidities and between complications and in-hospital mortality and duration of hospitalization. Results: Among 21,597 qualifying patients, 777 had vascular or nerve injuries or local infections, but only 41 (incidence 0.19% [95% CI, 0.14 to 0.26%]) were potentially consequent to brachial arterial cannulation. Vascular complications occurred in 33 patients (0.15% [0.10 to 0.23%]). Definitely or possibly related infection occurred in 8 (0.04% [0.02 to 0.08%]) patients. There were no plausibly related neurologic complications. Peripheral arterial disease was associated with increased risk of complications. Brachial catheter complications were associated with prolonged hospitalization and in-hospital mortality. Conclusions: Brachial artery cannulation for hemodynamic monitoring during cardiac surgery rarely causes complications.

CASE 5—2016Complex Congenital Cardiac Surgery in an Adult Patient With Hereditary Spherocytosis: Avoidance of Massive Hemolysis Associated With Extracorporeal Circulation in the Presence of Red Blood Cell Fragility

XTRACORPOREAL CIRCULATORY support among patients with genetic disorders producing erythrocyte fragility requires specific considerations involving decreasing shear stresses on red blood cells (RBCs) and vigilant intraoperative and postoperative monitoring for catastrophic hemolytic anemia. Hereditary spherocytosis (HS) is an autosomal dominant hemolytic anemia characterized by spheroid-shaped erythrocytes with increased osmolality and rigidity. Clinical presentation of HS varies depending on genetic penetrance. Decreased flexibility within the RBC membrane limits deformation and increases the possibility of hemolysis. Specifically, the mechanical stress of cardiopulmonary bypass (CPB) on HS erythrocytes presents a challenge during cardiac surgery. Although previous case reports of successful use of CPB during cardiac surgery in HS patients have been published, 1-13 significant perioperative hemolysis also has been reported. 6 The authors report the successful use of CPB in an adult HS patient undergoing multiple complex cardiac congenital repairs and review perioperative concerns and management.

Turbulence in the left ventricular outflow tract caused by an eccentric mitral inflow jet masquerades as aortic regurgitation.

January 2014 • Volume 118 • Number 1 A 48-year-old woman with a previous mechanical bileaflet mitral valve replacement was diagnosed with severe mitral stenosis and moderately severe aortic regurgitation by transthoracic echocardiography. She was referred to our institution for surgical replacement of her aortic and mitral valves. Our IRB waived the requirement for patient consent for this report. In the operating room after anesthetic induction, a transesophageal echocardiographic (TEE) midesophageal 4-chamber view confirmed an immobile mechanical mitral valve leaflet causing severe mitral stenosis (Video 1, see Supplemental Digital Content 1, http://links.lww.com/ AA/A679). Mean transmitral pressure gradient measured with continuous wave Doppler was 19 mm Hg with a heart rate of 55 bpm. A midesophageal long-axis view with color flow Doppler demonstrated severe turbulence in the left ventricular outflow tract (LVOT) during diastole, suggesting severe aortic regurgitation (Fig. 1; Video 2, see Supplemental Digital Content 2, http://links.lww.com/AA/A680). A midesophageal aortic valve short-axis view (partially cut through the LVOT) suggested aortic regurgitation (Video 3, see Supplemental Digital Content 3, http://links.lww. com/AA/A681). Significant shadowing from the mechanical mitral valve created difficulty in determining whether the jet resulted from aortic regurgitation or mitral inflow. Thus, other echocardiographic measures to differentiate the etiology of the diastolic LVOT turbulence were performed. A deep transgastric long-axis view which allowed imaging of the LVOT without shadowing from the prosthetic mitral valve demonstrated absence of turbulence proximal to the aortic valve, suggesting that LVOT turbulence did not originate from the aortic valve. Furthermore, spectral Doppler demonstrated LVOT flow, which peaked at less than 2.0 m/s and followed mitral valve opening (rather than aortic valve closing), consistent with mitral inflow (Fig. 2). Additional echocardiographic evidence inconsistent with severe aortic regurgitation was documented, including aortic valve leaflets without significant abnormalities, a normal-appearing aortic root, and absence of flow reversal in the descending aorta. These findings suggested that diastolic LVOT turbulence was related to an eccentric mitral inflow jet, rather than aortic regurgitation. The patient underwent mitral valve replacement with a 27-mm St. Jude bileaflet mechanical mitral valve (St. Jude Medical, St. Paul, MN). TEE performed after separation from cardiopulmonary bypass demonstrated a well-seated mitral valve and a competent aortic valve.