Increased blood transfusion and its impact in patients having tracheostomy while on extracorporeal membrane oxygenation.

INTRODUCTION: Tracheostomy has been utilized in combination with venovenous extracorporeal membrane oxygenation (VV-ECMO) to enable early spontaneous breathing and minimize sedation requirements. Tracheostomy has been previously reported to be safe in patients supported on VV-ECMO; however, the impact of tracheostomy on blood loss in VV-ECMO patients is unknown. METHODS: We analyzed VV-ECMO patients with and without tracheostomy over a 5-year period. In order to avoid other potential sources of blood loss not related to tracheostomy or ECMO-related blood loss, patients who underwent a recent surgery prior to ECMO or during ECMO (other than tracheostomy) were excluded. RESULTS: Sixty-three patients meeting the inclusion criteria were identified (tracheostomy n=30, non-tracheostomy n=33). Tracheostomy patients were found to require more daily transfusions of red blood cells (RBC) (0.47 [0.20-1.0] vs. 0.23 [0.06-0.40] units/day, p=0.02) and total blood products (0.60 [0.32-1.0] vs. 0.31 [0.10-0.50] units/day, p=0.01). CONCLUSIONS: These results suggest that tracheostomy while on VV-ECMO predisposes patients to increased transfusion burden. Based on previous research, this increased transfusion burden could potentially be linked to increased complications and mortality.

The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines-Anticoagulation During Cardiopulmonary Bypass.

Despite more than a half century of "safe" cardiopulmonary bypass (CPB), the evidence base surrounding the conduct of anticoagulation therapy for CPB has not been organized into a succinct guideline. For this and other reasons, there is enormous practice variability relating to the use and dosing of heparin, monitoring heparin anticoagulation, reversal of anticoagulation, and the use of alternative anticoagulants. To address this and other gaps, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiologists, and the American Society of Extracorporeal Technology developed an Evidence Based Workgroup. This was a group of interdisciplinary professionals gathered to summarize the evidence and create practice recommendations for various aspects of CPB. To date, anticoagulation practices in CPB have not been standardized in accordance with the evidence base. This clinical practice guideline was written with the intent to fill the evidence gap and to establish best practices in anticoagulation therapy for CPB using the available evidence. To identify relevant evidence, a systematic review was outlined and literature searches were conducted in PubMed using standardized medical subject heading (MeSH) terms from the National Library of Medicine list of search terms. Search dates were inclusive of January 2000 to December 2015. The search yielded 833 abstracts, which were reviewed by two independent reviewers. Once accepted into the full manuscript review stage, two members of the writing group evaluated each of 286 full papers for inclusion eligibility into the guideline document. Ninety-six manuscripts were included in the final review. In addition, 17 manuscripts published before 2000 were included to provide method, context, or additional supporting evidence for the recommendations as these papers were considered sentinel publications. Members of the writing group wrote and developed recommendations based on review of the articles obtained and achieved more than two thirds agreement on each recommendation. The quality of information for a given recommendation allowed assessment of the level of evidence as recommended by the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Recommendations were written in the three following areas: (1) heparin dosing and monitoring for initiation and maintenance of CPB; (2) heparin contraindications and heparin alternatives; and (3) reversal of anticoagulation during cardiac operations. It is hoped that this guideline will serve as a resource and will stimulate investigators to conduct more research and to expand on the evidence base on the topic of anticoagulation therapy for CPB.

Outcomes of lobar and sublobar resections for non-small-cell lung cancer: a single-center experience.

OBJECTIVES: Lung cancer is the leading cause of cancer-related mortality in the United States. Kentucky has the highest age-adjusted lung cancer rate and has one of the highest death rates from lung cancer in the country. Lobectomy is considered the standard therapy for non-small-cell lung cancer (NSCLC), whereas sublobar resection remains an option for selected patients. We investigated outcomes in patients having standard resections for lung cancer (lobectomy) compared with those having sublobar resections in a population with high prevalence of, and with a high death rate from, lung cancer. METHODS: We studied patients having lung cancer resections at the University of Kentucky between 2002 and 2007. We reviewed the records of 222 patients who had either lobar or sublobar resections for NSCLC. This retrospective review identified key outcome variables, as well as short- and long-term survival. Propensity analysis allowed outcome comparison between patients having lobar and sublobar resections matched for preoperative variables. RESULTS: Of the 222 study patients, 181 patients had lobectomies and 41 had sublobar resections. For all resections, lobectomy was associated with improved 1-, 3-, and 5-year survival rates compared with sublobar resections. Compared with patients having sublobar resections, lobectomy patients had significantly increased unadjusted perioperative morbidity (43.1% lobectomy vs 7.3% sublobar), but not mortality. After propensity analysis, sublobar resection predicted significantly reduced morbidity (6.3% vs 53.3%, P < 0.001), but not operative mortality (3.3% vs 3.3%, P = not significant), compared with lobectomy in patients matched for age, sex, cancer stage, and date of operation. Adjuvant chemotherapy combined with radiation therapy showed significantly improved long-term survival for either type of resection. Cox regression with adjustment for age, cancer stage, and postoperative complications suggested that neoadjuvant chemotherapy/radiotherapy increased long-term survival (P = 0.038, hazard ratio 0.49). CONCLUSIONS: Sublobar resections for NSCLC have less morbidity compared with lobectomy, but at the cost of decreased long-term survival. These results imply that surgeons select patients for lobar or sublobar resections based on physiologic and functional parameters, and that differences in outcomes between these two groups reflect this selection bias. We suspect that these results are typical of surgical treatment of NSCLC in a heterogeneous high-risk population with a high penetration and prevalence of lung cancer.

Modern management of thoracic empyema.

OBJECTIVES: Historically, surgical management of empyema was performed predominantly via open thoracotomy; however, during the past decade the use of video-assisted thoracoscopic surgery (VATS) as an alternative has increased. This study retrospectively compared the outcomes and management of patients with empyema at the University of Kentucky Medical Center who had undergone VATS versus those receiving open thoracotomy to determine whether VATS decortication provided comparable results. METHODS: Adult patients who had undergone open thoracotomy or VATS decortication for empyema between 2005 and 2009 at the University of Kentucky were identified by querying the hospital's cardiothoracic surgery database. Patients were sorted by procedure on an intent-to-treat basis. Comorbid conditions, preoperative course, operative outcomes, and postoperative outcomes were compared. Quantitative data were analyzed with either an unpaired t test or the Mann-Whitney U test. Qualitative data were analyzed using the Fisher exact test. RESULTS: Fifty-three patients were identified, 18 of whom underwent VATS and 35 underwent open thoracotomy. Eight of the 18 VATS procedures (44.4%) were converted to open thoracotomy. Patients undergoing VATS had a significantly shorter median length of stay (11 vs 18 days, respectively; P = 0.044), chest tube duration (6 vs 12 days, respectively; P < 0.001), operative blood loss (55.6 vs 344 mL, respectively; P = 0.003), and fewer postoperative respiratory failures (0% vs 22.9%, respectively; P = 0.0451). The two groups did not differ significantly in overall morbidity, reoperation, mortality, or preoperative comorbidities. CONCLUSIONS: In adults, VATS offers results comparable to those of open thoracotomy, and lengths of stay, chest tube durations, and postoperative outcomes are superior. Although the conversion rate of VATS to open thoracotomy at our institution was high (38.1%) compared with studies at other institutions, the data still indicate that VATS is both a safe and reliable alternative to open thoracotomy.

Intraoperative blood transfusion of one or two units of packed red blood cells is associated with a fivefold risk of stroke in patients undergoing elective carotid endarterectomy.

OBJECTIVE: Transfused blood can disrupt the coagulation cascade. We postulated that packed red blood cell (PRBC) transfusion may be associated with thromboembolic phenomena. We used propensity matching to examine the relationship between intraoperative PRBC transfusion and stroke during carotid endarterectomy (CEA). METHODS: We selected CEA procedures from the American College of Surgeons National Surgical Quality Improvement Program database from 2005-2009. We excluded bilateral, redo, and emergent procedures. We used multivariate logistic regression to identify independent risk factors for stroke. We then calculated a transfusion propensity score to match patients who received one or two units of transfused PRBC intraoperatively with patients of similar risk profiles who had not been transfused. RESULTS: Our criteria resulted in 12,786 elective CEA patients. Of these, 82 (0.6%) received a one- to two-unit intraoperative transfusion. Thirty-day stroke rates were 1.4% (179/12,704) in the nontransfused group and 6.1% (5/82) in the transfused group (Fisher exact test, P = .007). In forward stepwise multivariable regression of risk factors, only hemiplegia, stroke history, and transient ischemic attacks were predictive of 30-day stroke. We used these same variables to calculate transfusion propensity. We matched 80 transfused patients with 160 controls, thus, creating two groups with very similar risk profiles differing only by their transfusion status. In the matched groups, there was a fivefold increase in the risk of stroke in transfused patients (Fisher exact test, P = .043) CONCLUSIONS: Intraoperative transfusion of one to two units of PRBCs is associated with a fivefold increase in stroke risk. This holds true after consideration of stroke risk variables and operative duration as a surrogate for technical difficulty. The increased risk may be related to several effects of transfused blood on the coagulation inflammation cascade.

Surgical treatment of lung cancer in octogenarians.

BACKGROUND: As the population ages, octogenarians are becoming the fastest growing patient demographic for non-small-cell lung cancer. We examined lobectomies and 30-day outcomes in this group compared with younger patients to gain insight into the optimal treatment for this challenging group. METHODS: We analyzed data from the American College of Surgeons National Quality Improvement Program for patients with lung cancer undergoing lobectomy during calendar years 2005-2010. We compared clinical risk factors, intraoperative factors, and 30-day operative mortality and major morbidity in octogenarians versus younger patients undergoing either open traditional thoracotomy (OPEN) or video-assisted (VATS) pulmonary lobar resection. RESULTS: Of 2171 patients who had lobar resections for lung cancer, 245 (11%) were octogenarians. Six hundred eight lobectomies (28.0%) were VATS procedures and 1563 (72.0%) were OPEN procedures. The VATS rate increased as patient age increased (34% VATS for octogenarians vs 27% for patients younger than 80 years; P = 0.01). Thoracic surgeons performed VATS with greater frequency compared with general surgeons, especially in octogenarians (41% VATS for thoracic surgeons vs 29% for general surgeons; P < 0.001). Univariate analysis suggests significantly increased major morbidity (pulmonary, renal, and sepsis), but not operative mortality in octogenarians; however, multivariate predictors of major morbidity include OPEN procedures, preoperative decreased functional status, history of chronic obstructive pulmonary disease, preoperative sepsis, prior radiation, diabetes, and dyspnea on exertion (all P < 0.05), but they do not include advanced age. CONCLUSIONS: Comorbidities predict most increased morbidity in octogenarians, and advanced age per se is not an important multivariate predictor of postoperative morbidity or mortality. The frequency of VATS lobectomy increased with increasing patient age, and VATS predisposes to decreased morbidity in octogenarians.

Mediastinoscopy: trends and practice patterns in the United States.

OBJECTIVES: Historically, mediastinoscopy has been the gold standard for the staging of lung cancer. A practice gap exists as the result of a variation in knowledge concerning current trends and practice patterns of mediastinoscopy usage. In addition, there are regional variations in practice-based learning and patient care. Lessons learned during surgeries performed on patients with lung cancer and other advances such as positron emission tomography and endobronchial ultrasound could be universally applied to improve surgeons' management of patient care. The purpose of this study was to assess contemporary practices in the staging of lung cancer. METHODS: We queried the Society of Thoracic Surgeons National Database for data regarding mediastinoscopy usage, yield, and variation, both by year and region. RESULTS: Cases with mediastinoscopy, as a percentage of all cases performed in the database, have significantly decreased from 14.6% in 2006 to 11.4% in 2010 (P < 0.001). The 5-year median rate of mediastinoscopy in lung cancer patients at 163 centers was 15.3% (interquartile range 5.2%-31.7%), indicating significant variation among centers. The overall median center rate also decreased over time from 21.4% (2006) to 10.0% (2010). CONCLUSIONS: With advances in minimally invasive procedures and imaging, mediastinoscopy usage has declined significantly. Our findings are likely to be relevant to both clinical practice and practice guidelines.

Failure to Rescue: A New Society of Thoracic Surgeons Quality Metric for Cardiac Surgery.

BACKGROUND: Failure to rescue (FTR) focuses on the ability to prevent death among patients who have postoperative complications. The Society of Thoracic Surgeons (STS) Quality Measurement Task Force has developed a new, risk-adjusted FTR quality metric for adult cardiac surgery. METHODS: The study population was taken from 1118 STS Adult Cardiac Surgery Database participants including patients who underwent isolated CABG, aortic valve replacement with or without CABG, or mitral valve repair or replacement with or without CABG between January 2015 and June 2019. The FTR analysis was derived from patients who had one or more of the following complications: prolonged ventilation, stroke, reoperation, and renal failure. Data were randomly split into 70% training samples (n = 89,059) and 30% validation samples (n = 38,242). Risk variables included STS predicted risk of mortality, operative procedures, and intraoperative variables (cardiopulmonary bypass and cross-clamp times, unplanned procedures, need for circulatory support, and massive transfusion). RESULTS: Overall mortality for patients undergoing any of the index operations during the study period was 2.6% (27,045 of 1,058,138), with mortality of 0.9% (8316 of 930,837), 8% (7618 of 94,918), 30.6% (8247 of 26,934), 51.9% (2661 of 5123), and 62.3% (203 of 326), respectively, among patients having none, one, two, three, or four complications. The FTR risk model calibration was excellent, as were model discrimination (c-statistic 0.806) and the Brier score (0.102). Using 95% Bayesian credible intervals, 62 participants (5.6%) performed worse and 53 (4.7%) performed better than expected. CONCLUSIONS: A new risk-adjusted FTR metric has been developed that complements existing STS performance measures. The metric specifically assesses institutional effectiveness of postoperative care, allowing hospitals to target quality improvement efforts.

Antiplatelet drugs: mechanisms and risks of bleeding following cardiac operations.

Preoperative antiplatelet drug use is common in patients undergoing coronary artery bypass grafting (CABG). The impact of these drugs on bleeding and blood transfusion varies. We hypothesize that review of available evidence regarding drug-related bleeding risk, underlying mechanisms of platelet dysfunction, and variations in patient response to antiplatelet drugs will aid surgeons as they assess preoperative risk and attempt to limit perioperative bleeding. The purpose of this review is to (1) examine the role that antiplatelet drugs play in excessive postoperative blood transfusion, (2) identify possible mechanisms to explain patient response to antiplatelet drugs, and (3) formulate a strategy to limit excessive blood product usage in these patients. We reviewed available published evidence regarding bleeding risk in patients taking preoperative antiplatelet drugs. In addition, we summarized our previous research into mechanisms of antiplatelet drug-related platelet dysfunction. Aspirin users have a slight but significant increase in blood product usage after CABG (0.5 U of nonautologous blood per treated patient). Platelet adenosine diphosphate (ADP) receptor inhibitors are more potent antiplatelet drugs than aspirin but have a half-life similar to aspirin, around 5 to 10 days. The American Heart Association/American College of Cardiology and the Society of Thoracic Surgeons guidelines recommend discontinuation, if possible, of ADP inhibitors 5 to 7 days before operation because of excessive bleeding risk, whereas aspirin should be continued during the entire perioperative period in most patients. Individual variability in response to aspirin and other antiplatelet drugs is common with both hyper- and hyporesponsiveness seen in 5 to 25% of patients. Use of preoperative antiplatelet drugs is a risk factor for increased perioperative bleeding and blood transfusion. Point-of-care tests can identify patients at high risk for perioperative bleeding and blood transfusion, although these tests have limitations. Available evidence suggests that multiple blood conservation techniques benefit high-risk patients taking antiplatelet drugs before operation. Guidelines for patients who take aspirin and/or thienopyridines before cardiac procedures include some or all of the following: (1) preoperative identification of high-risk patients using point-of-care testing; (2) withdrawal of aspirin or other antiplatelet drugs for a few days and delay of operation in patients at high risk for bleeding if clinical circumstances permit; (3) selective perioperative use of evidence-based blood conservation interventions (e.g., short-course erythropoietin, off-pump procedures, and use of intraoperative blood conservation techniques), especially in high-risk patients; and (4) platelet transfusions if clinical bleeding occurs.

Effectiveness of tunneled pleural catheter placement in patients with malignant pleural effusions.

Pleural effusions (PE) occur frequently among patients with various types of advanced malignancies, resulting in remarkably decreased quality of life. Treatment of malignant PE includes placement of a chest tube with subsequent placement of a tunneled pleural catheter. We reviewed our experience with tunneled pleural catheter use to assess outcomes and resource utilization of this intervention. A retrospective study of consecutive patients (n = 163, including 41 outpatients) who were treated between July 2001 and April 2008 with tunneled pleural catheters was performed to evaluate operative and discharge outcomes. The average age of the patients was 59.32 years (range: 24 to 89). Lung cancer, breast cancer, and ovarian cancer were common primary diseases in this patient population. The mean hospital stay after tunneled pleural catheter placement was 3.19 days (range: 0 to 56), with 41 patients treated as outpatients. Thirteen inpatient deaths were related to the patients' primary diseases, but no deaths were due to drain placement itself. Eight patients (4.91%) required reoperation to replace a nonfunctioning drain or to add an additional drain, and six patients underwent a second procedure to place a contralateral drain. One hundred twenty-six patients (77.30%) were discharged home following the procedure and hospital stay. Fifty-five people achieved spontaneous pleurodesis. Tunneled pleural catheter placement is a safe and effective approach to the treatment of PE. The advantages of tunneled pleural catheter placement include symptomatic relief and improved quality of life. This method allows patients to spend time at home with their family and avoid prolonged hospitalization.

The dangers of gathering data: surgeon-specific outcomes revisited.

The accuracy of risk adjustment is important in developing surgeon profiles. As surgeon profiles are obtained from observational, nonrandomized data, we hypothesized that selection bias exists in how patients are matched with surgeons and that this bias might influence surgeon profiles. We used the Society of Thoracic Surgeons risk model to calculate observed to expected (O/E) mortality ratios for each of six cardiac surgeons at a single institution. Propensity scores evaluated selection bias that might influence development of risk-adjusted mortality profiles. Six surgeons (four high and two low O/E ratios) performed 2298 coronary artery bypass grafting (CABG) operations over 4 years. Multivariate predictors of operative mortality included preoperative shock, advanced age, and renal dysfunction, but not the surgeon performing CABG. When patients were stratified into quartiles based on the propensity score for operative death, 83% of operative deaths (50 of 60) were in the highest risk quartile. There were significant differences in the number of high-risk patients operated upon by each surgeon. One surgeon had significantly more patients in the highest risk quartile and two surgeons had significantly less patients in the highest risk quartile (p < 0.05 by chi-square). Our results show that high-risk patients are preferentially shunted to certain surgeons, and away from others, for unexplained (and unmeasured) reasons. Subtle unmeasured factors undoubtedly influence how cardiac surgery patients are matched with surgeons. Problems may arise when applying national database benchmarks to local situations because of this unmeasured selection bias.

Is Internal Mammary to the Anterior Descending Always the Best Option?

The left internal mammary artery (LIMA) is the gold standard conduit used to revascularize the left anterior descending artery and has consistently been shown to be associated with better survival, graft patency, and freedom from cardiac events compared with other used conduits. Evaluation of LIMA flow and anatomy is not routinely done by the interventional cardiologist while performing the left heart catheterization. We present a case where the LIMA was found to be the major blood supply to the left leg, which might have led to leg ischemia if the LIMA had been used as graft.

The relationship between mortality and preexisting cardiac disease in 5,971 trauma patients.

BACKGROUND: We observed significant morbidity and mortality in patients with preexisting cardiac disease who suffer severe traumatic injuries. We wondered about the types of injury seen and about the cardiac risks factors that predispose to worse outcomes in these patients. Our hypothesis is that significant cardiac comorbidity is associated with adverse trauma outcomes. METHODS: We reviewed 10,144 trauma admissions to the University of Kentucky during a 5-year period (2002-2007) in patients 21 years or older. The types and extent of injuries were characterized, and risk factors for poor outcome were assessed. Propensity analysis assessed variable interaction and adjusted for important multivariate cardiovascular risk factors. RESULTS: Of the 10,144 adult trauma patients, there was adequate cardiovascular history before emergency treatment in 5,971 patients (58.9%). Of the 700 trauma deaths, 236 (33.7%) had adequate medical history to allow accurate assessment of cardiovascular disease. Significant multivariate predictors of trauma-related death included older age (odds ratio [OR] = 0.938), injury severity score (OR = 0.893 per unit score), major burn (OR = 5.907), assault with a weapon (OR = 3.205), systolic blood pressure divided by Glasgow coma score (OR = 0.958 per score unit), and female (OR = 1.629). In the cohort of 236 deaths with adequate medical history, severe head and chest injuries caused death in 187 patients (79.2%). Significant propensity-adjusted cardiovascular risks of trauma death included preinjury warfarin use (OR = 2.309, p = 0.001), congestive heart failure (CHF) (OR = 2.060, p = 0.011), and preinjury beta-blocker use (OR = 2.62, p = 0.001). The highest mortality rates occurred in patients with combinations of these cardiovascular risk factors. For example, patients on warfarin with CHF had a 26.3% mortality rate, whereas patients on warfarin and beta-blocker had a 27.3% mortality rate. CONCLUSIONS: Preinjury cardiac risk factors, especially preinjury warfarin, beta-blocker use, and CHF, are independent multivariate predictors of mortality in patients suffering significant trauma. Although head and chest injuries are the most frequent causes of death, patients with more than one preinjury cardiac risk factor have 5 to 10 times the mortality risk compared with those without cardiac risks.

Pulmonary Artery Stent Graft Repair of Bronchovascular Fistula.

Endobronchial stenting is a well-established palliative approach in lung cancer patients with airway obstruction secondary to tumor burden. However endobronchial stenting can be complicated by stent erosion into adjacent vessels. Although most cases of endobronchial stent-related hemoptysis can be treated by stent revision and/or surgical resection, here we present a case managed by endovascular pulmonary arterial stent placement as a last resort option in the management of an iatrogenic bronchovascular fistula in a nonsurgical candidate.

Bundled Payments for Surgical Care-More Questions Than Answers.

Bundled payment models assign financial responsibility for extended episodes of care up to 90 days after operation. The report by Koeckert et al, in this issue, describes 376 patients having either transcatheter aortic valve replacements or surgical aortic valve replacements. They investigated the impact of readmissions on the Bundled Payments for Care Improvement initiative (BPCI) payment for Medicare valve patients. The authors' hospital was designated as a BPCI institution that linked reimbursement to the different phases of care (in-patient, outpatient follow-up, emergency visits, and other postacute care) up to 90 days after operation. They found that bundled costs were significantly increased above BPCI reimbursements in readmitted patients, especially transcatheter aortic valve replacements patients who were readmitted late up to 90 days after operation. This apparent disconnect between BPCI reimbursement and actual costs raises questions about BPCI reimbursement.

Meta-Analysis of Acetylsalicylic Acid Desensitization in Patients With Acute Coronary Syndrome.

Acetylsalicylic acid (ASA) hypersensitivity represents a clinical challenge in acute coronary syndrome (ACS) patients urgently requiring ASA for antiplatelet therapy. ASA desensitization has been reported with successful outcomes in cardiac patients. The aim of this review is to determine the safety and efficacy of ASA desensitization therapy in ACS patients. A PubMed database search was conducted for articles containing combinations of keywords, "aspirin desensitization" or "aspirin hypersensitivity" and "acute coronary syndrome" between January 1, 1990 and August 1, 2018. The primary end point was desensitization protocol success. Secondary end points included hypersensitivity adverse events and ASA discontinuation due to hypersensitivity adverse events at follow-up. Fifteen reports consisting of 480 ACS patients with previous hypersensitivity to ASA were included. The pooled desensitization success rate was 98.3% (95% confidence interval: 97.2% to 99.5%). There was no statistical difference in outcomes between protocols ≤ 2 hours and > 2 hours in duration (96.3[92.3 to 100.3]% vs 97.2[94.6 to 99.8]%; p = 0.71). Protocols with > 6 dose escalations were associated with higher success rates compared to those with ≤ 6 doses (99.2[97.9 to 100.4]% vs 95.4[93 to 97.8]%; p = 0.007). At follow-up between 1 and 46 months (mode 12 months), zero hypersensitivity adverse events were reported. Consequently, no ASA discontinuations were related to hypersensitivity adverse events. In conclusion, ASA desensitization therapy is safe and effective in patients with ACS. Protocols with > 6 dose escalations may be optimal for ASA desensitization in ACS patients.