Andrej Alfirevic

Recombinant Factor VII Is Associated With Worse Survival in Complex Cardiac Surgical Patients

BACKGROUND Recombinant activated factor VII (rFVIIa) decreases requirements for allogeneic blood transfusion and chest reexploration in patients undergoing cardiac surgery. Whether rFVIIa increases the risk of postoperative adverse events is unclear. We tested whether rFVIIa administration was associated with increased mortality and neurologic and renal morbidity in patients undergoing cardiac surgery. Risk of thromboembolic complications and the dose-response of rFVIIa on mortality and morbidity were also evaluated. METHODS Of 27,977 patients who had complex cardiac surgery, 164 patients (0.59%) received rFVIIa perioperatively. Using propensity-matching techniques, patients were matched to a maximum of 3 control patients. Patients who received rFVIIa were compared with control patients on risk of mortality, neurologic and renal morbidity, and thromboembolic complications, including a composite of myocardial infarction, pulmonary embolism, and deep venous thrombosis. A corresponding dose-response analysis using multivariable logistic regression was also performed. RESULTS Propensity techniques successfully matched 144 patients (88%) with 359 control patients. Of patients who received rFVIIa, 40% experienced in-hospital mortality compared with 18% of control patients (odds ratio, 2.82; 98.3% confidence interval, 1.64 to 4.87; p<0.001). Furthermore, 31% of patients treated with rFVIIa versus 17% of control patients experienced renal morbidity (odds ratio, 2.07; 98.3% confidence interval, 1.19 to 3.62; p=0.002); however, neurologic morbidity and thromboembolic complications were not different among groups. High-dose rFVIIa (>60 μg/kg) did not increase the risk for mortality compared with treatment with low-dose rFVIIa (<60 μg/kg). CONCLUSIONS Administration of rFVIIa is associated with increased mortality and renal morbidity in patients undergoing cardiac surgery.

Transfusion Increases the Risk for Vasoplegia After Cardiac Operations

BACKGROUND Perioperative vasoplegia is associated with increased morbidity. Red blood cell (RBC) transfusion increases plasma concentrations of inflammatory mediators, possibly contributing to the development of vasoplegia. We investigated the prevalence of mild and profound postoperative vasoplegia, identified factors associated with its development, and examined the role of RBC and component transfusion on the occurrence of postoperative vasoplegia. METHODS Between January 1, 2000, and January 1, 2007, 25,960 patients underwent on-bypass cardiac surgical procedures. The incidence of vasoplegia was defined as (1) mild vasoplegia requiring norepinephrine infusion for blood pressure support on the day of operation and postoperative day 1, and (2) profound vasoplegia requiring vasopressin, with or without concomitant norepinephrine infusion, on the day of operation and postoperative day 1. Separate logistic regression models were used to model risk factors for development of mild and profound vasoplegia. RESULTS RBC transfusion increased risk-adjusted odd ratios (ORs) of developing mild vasoplegia (1.07 [95% confidence limits (CL), 1.05, 1.10]; p<0.001) and profound vasoplegia (1.38 [1.31, 1.46] p<0.001). The risk-adjusted ORs (95% CL) for mild vasoplegia and profound vasoplegia were similarly increased by fresh-frozen plasma (OR, 1.24 [1.10, 1.41], p<0.001; and OR, 1.20 [1.13, 1.29], p<0.001) and platelet transfusion (OR, 1.39 [1.25, 1.54], p<0.001; and OR, 1.22 [1.14, 1.31], p<0.001), respectively. CONCLUSIONS Red blood cells, fresh-frozen plasma, and platelet transfusion increased the prevalence of vasoplegia. RBC transfusion exhibited a dose-dependent response for developing vasoplegia with each RBC unit transfused. Further investigation is necessary to determine whether prophylactic use of vasopressor support in the setting of transfusion can ameliorate risk and effect outcomes.

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.

Single center TAVR experience with a focus on the prevention and management of catastrophic complications

Transcatheter aortic valve replacement (TAVR) is an important treatment option for patients with severe symptomatic aortic stenosis (AS) who are inoperable or at high risk for complications with surgical aortic valve replacement. We report here our single‐center data on consecutive patients undergoing transfemoral (TF) TAVR since the inception of our program, with a special focus on minimizing and managing complications.

Pressure sore as a complication of labor epidural analgesia.

UNLABELLED Lumbar epidural analgesia has become a common mode of pain control for laboring patients. Side effects, such as hypotension, motor blockade, respiratory depression, dural puncture, and urinary retention, are well described. Although pressure sores have been thought of as a complication limited to elderly, emaciated, unconscious, or bedridden patients, we describe the occurrence of pressure sores in a young and healthy parturient after lumbar epidural analgesia. IMPLICATIONS We report a pressure sore that resulted from lumbar epidural analgesia for labor.

Failed closure of paravalvular leak with an amplatzer occluder device after mitral valve replacement.

A 64-yr-old man presented for surgical intervention of a persistent paravalvular mitral valve (MV) regurgitant leak. The patient’s medical history included aortic valve (AV) and MV replacement surgery with mechanical prosthesis 2 yr before the current presentation. His postoperative course had been complicated by anemia and gastrointestinal bleeding, requiring multiple red blood cell transfusions. Further evaluation revealed a gastric arteriovenous malformation and chronic renal insufficiency. In addition, the patient was found to have a MV paravalvular leak associated with hemolytic anemia. Due to the patient’s co-morbidities, the paravalvular leak was closed using a percutaneous catheter approach with an Amplatzer® muscular ventricular septal defect occluder device (AGA Medical Corporation, Golden Valley, MN). Several months after closure, the patient reported symptoms of shortness of breath and was found to have profound anemia, predominantly hemolytic in origin (decreased haptoglobin, elevated lactate dehydrogenase). A transthoracic echocardiogram was indeterminant due to suboptimal image quality from the patient’s profound obesity. A subsequent transesophageal echocardiogram (TEE) revealed the presence of the occluder device and a moderately-severe MV paravalvular regurgitant jet; the mechanical AV prosthesis was intact. Intraoperative TEE confirmed preoperative findings of mechanical bi-leaflet MV prosthesis, which was wellseated in the valve annulus without accompanied “rocking” motion. A moderately-severe paravalvular MV leak was noticed around the Amplatzer device. The device itself was malpositioned and shifted from the proper horizontal and parallel position of both occluder disks with the valvular annular plane to an angle directed improperly toward the left atrium (Figs. 1 and 2 and Video clips 1 and 2; please see video clips available at www.anesthesia-analgesia.org). The patient underwent an uneventful reoperation for replacement of both the AV and MV with bioprosthesis (Video clip 3; please see video clips available at www.anesthesia-analgesia.org). The decision to replace the AV mechanical prosthesis was made preoperatively to avoid potential postoperative gastrointestinal bleeding episodes secondary to anticoagulation. The incidence of paravalvular regurgitation after primary MV replacement with mechanical or bioprosthetic valves is reported to be 12.5%. The paravalvular regurgitation developing in the nonimmediate postoperative period may be secondary to suture dehiscence or as a consequence of valvular endocarditis. In comparison to sometimes technically difficult transthoracic echocardiography, TEE offers improved sensitivity for detection of paravalvular regurgitant jets. Reported indications for use of percutaneous techniques as a treatment option for patients with paravalvular leaks include patients with severe heart failure, transfusion-dependent hemolysis and patients requiring prolonged postoperative ventilatory support. Percutaneous techniques with the use of the Amplatzer occluder device have been described in the literature for closure of paravalvular regurgitant jets in patients unfit for surgery because of the high procedural risk. Cortes et al. described a case series documenting successful implantation of the Amplatzer device with minimal associated patient morbidity. Immediate postdeployment complications may include interference of normal prosthetic valve leaflet motion, i.e., preventing prosthesis opening, thrombus formation as well as residual atrial septal defect after the transseptal approach. Device dislodgment has been reported as a late complication of the procedure. This article has supplementary material on the Web site: www.anesthesia-analgesia.org.

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.

Carinal resection using an airway exchange catheter-assisted venovenous ECMO technique.

To the Editor, Airway management during tracheal resection is one of the great challenges confronting anesthesiologists, especially when carinal resection is involved. When ventilation through the mainstem bronchi is not an option due to surgical exposure, extracorporeal oxygenation techniques become a vital tool. Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a preferred mode of assuring adequate oxygenation in patients with normal right ventricular function. However, its oxygenation efficacy is lower than either cardiopulmonary bypass (CPB) or venoarterial ECMO (VA-ECMO). We describe herein a case where an airway exchange catheter (AEC) was effective in assisting oxygenation during carinal resection with VV-ECMO. A 52-yr-old male presented with hoarseness, chronic cough, and hemoptysis. Flexible bronchoscopy revealed a squamous cell carcinoma located in the distal trachea just proximal to the carina and occluding about 50% of the tracheal lumen. The patient’s medical history was significant for hypertension, gastroesophageal reflux disease, and lumbar disc displacement. Preoperative pulmonary function tests showed a reduced FEV1/FVC ratio compatible with mild airflow obstruction, normal diffusion capacity, and normal measured lung volumes. Mediastinoscopy and distal tracheal and carinal resection with primary anastomosis were planned. In the operating room, after thoracic epidural catheter placement, general anesthesia was induced slowly with titration of sodium thiopental while the patient maintained spontaneous respiration. Once an adequate level of anesthesia was obtained using additional volatile anesthetic, a single-lumen endotracheal intubation was performed under direct laryngoscopy. Pancuronium was administered after adequate ventilation had been confirmed. Traditional lung isolation techniques were not an option due to the presence of the mass lesion at the carina and both main stem bronchi. Thus, the VV-ECMO was planned to assure adequate gas exchange during surgery. While the patient was in the supine position, mediastinoscopy was performed, followed by VV-ECMO cannula placement. The VV-ECMO was instituted via femoral and right internal jugular venous access with a flow rate of 3 L min. In order to assure proper cannula positioning to avoid recirculation phenomenon, the surgical team measured the location of the cannula tips from the insertion site. The patient was then repositioned into the left lateral decubitus position. The trachea and carina were dissected via the extended right thoracotomy incision. After the surgeon obtained adequate exposure to the trachea and carina, ventilation was stopped and VV-ECMO was initiated. With the VV-ECMO, the oxygen saturation persisted close to 80% (Table). At this point, a decision was made to insufflate supplemental oxygen to the patient’s lungs. With its flexibility and small size, a 14 Fr 100-cm soft-tip Cook Airway Exchange Catheter (Cook Medical, Bloomington, IN, USA) was inserted via the endotracheal tube into the right bronchus with a 6 L min oxygen insufflation through its lumen (Figure). We decided not to use a bronchial blocker due to the increased resistance to the gas flow and the possibility of lung overinflation from gas entrapment with the inflated balloon. Upon the completion of the right bronchial anastomosis, W. Keeyapaj, MD (&) Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit St., Boston, MA, USA e-mail: kworasak@yahoo.com

An unusual presentation of carcinoid tumor

A 75-yr-old man presented to the operating room for a right ventricular (RV) mass excision and tricuspid valve (TV) replacement. The patient reported progressive worsening of dyspnea on exertion associated with lower extremity swelling, abdominal distension, diarrhea, and several episodes of hallucinations. The preoperative evaluation and workup revealed the presence of a carcinoid tumor of the mesentery. This was supported by elevated liver function tests and a urine 5hydroxyindole-acetic acid level of 78.9 (normal 0–10 mg/24 h) as well as elevated serum serotonin level of 1050 ng/mL (normal 90–195 ng/mL). Computed tomography of the abdomen and pelvis demonstrated a 3.2 cm × 2.3 cm mesenteric soft tissue mass in the right lower quadrant.