Purpose: To determine the impact of preoperative aspirin on bleeding and other complications in patients undergoing robot-assisted radical prostatectomy and nephrectomy.
Patients and Methods: We identified all patients who underwent robot-assisted radical prostatectomy or robot-assisted nephrectomy by a single surgeon between August 2008 and August 2010. We compared patients in whom aspirin had not been administered for 7 days with those who received aspirin the morning of surgery. Patients on other antiplatelet agents or anticoagulants were excluded.
Results: Forty-four patients underwent prostatectomy without recent aspirin, and 51 received preoperative aspirin. There were no significant differences between the two groups in terms of age, body mass index, American Society of Anesthesiologists score, prostate-specific antigen level, or highest Gleason score. Operative time (182 vs 174 min, P=0.19), median blood loss (175 vs 100 mL, P=0.12), and duration of hospital stay (1 vs 1 day, P=0.08) were similar between the two groups, respectively. No patient received a transfusion. Three patients who had not received aspirin and one who had were readmitted within 30 days. In the nephrectomy cohort, 12 patients had not received aspirin and 14 had. There were no differences in median blood loss (65 vs 50 mL, P=0.96), median operative time (176 vs140 min, P=0.14), or median hospital stay (2 vs 2 days, P=0.74). No patient received a transfusion.
Conclusions: The administration of aspirin to patients undergoing robot-assisted radical prostatectomy and nephrectomy appears to be safe. The risk of cardiovascular complications resulting from stopping aspirin may exceed the risk of perioperative bleeding and associated complications.
Meta-analysis of several randomized studies indicates that aspirin reduces the risk of stroke and myocardial infarction by approximately one-third.1 Retrospective studies suggest that aspirin withdrawal precedes up to 10.2% of acute cardiovascular syndromes.1 In addition to its cardioprotective effect, aspirin has been found to reduce deaths from several common cancers, including prostate cancer. One study reported a 21% reduction in the risk of prostate cancer among aspirin users compared with nonusers.2
Nonetheless, the current most common practice, in many cases supported by published guidelines, is to discontinue aspirin and other forms of anticoagulation before major surgical procedures. Many patients undergoing surgery, however, including urologic surgery, have significant cardiovascular disease necessitating treatment with aspirin and are believed to be at increased cardiovascular risk when aspirin is held, particularly during a prothrombotic state such as surgery. The benefit of withholding aspirin may well be exceeded by the harm of doing so, particularly when less invasive surgical approaches, such as robot-assisted surgery, are used.
In November 2009, one surgeon at our institution (DR) changed his practice and continued or initiated aspirin in adult patients with a cancer diagnosis who were scheduled for prostate and kidney surgery and maintained it throughout the perioperative period, providing us with the opportunity to compare clinical outcomes of patients on and off aspirin. In this study, we aimed to analyze the operative and clinical outcomes of patients who underwent robot-assisted radical prostatectomy and robot-assisted radical nephrectomy before this date, off aspirin, and compare them with patients who underwent these procedures receiving aspirin.
Robotic surgery in urologic disease has gained popularity in the United States, and its application has extended beyond radical prostatectomy to a variety of surgeries, including radical nephrectomy, radical cystectomy, pyeloplasty, and many others. To our knowledge, this is the first evaluation of the safety of aspirin in the perioperative period for robot-assisted radical prostatectomy and robot-assisted nephrectomy.
In this Institutional Review Board approved,3 retrospective cohort study using electronic health records and a prospectively collected surgical database, we identified all patients who underwent a robot-assisted laparoscopic radical prostatectomy or robot-assisted laparoscopic radical nephrectomy by a single surgeon from August 2008 to August 2010. In November 2009, the clinical practice was changed to assure that all patients with vascular disease or at risk of vascular disease were maintained on aspirin through the surgical procedure. Thus, all patients operated on before November 2009 underwent surgery without aspirin and comprise the preaspirin cohort, and all patients who underwent surgery after November 2009 received aspirin and were analyzed as the aspirin cohort.
The aspirin cohort included any patient who was administered aspirin on the morning of surgery or continued aspirin before surgery. The preaspirin arm included any patient in which all antiplatelet agents were held in the 7 days before surgery. These patients were instructed to restart the aspirin 7 days after surgery. Patients who had received aspirin (n=2) or any other form of antiplatelet agent (n=0) or anticoagulant (n=1) (ie., heparin within 4 hours, enoxaparin within 18 hours, warfarin within 7 days, persantine within 7 days, or fondaparinux within 36 hours before surgery) were excluded from analysis. Patients with unknown aspirin status (n=3) were also excluded. None of the patients in either group were receiving corticosteroids, which may affect vessel fragility and the risk of bleeding.
All robot-assisted surgery was performed with the da Vinci S robotic surgical platform. For the radical prostatectomy, peritoneal access was obtained via the open Hassan technique. In addition, one 12-mm assistant port and three 8-mm robotic ports were placed in semicircle configuration at the level of the umbilicus. After transperitoneal access to the space of Retzius, the radical prostatectomy was performed with early control of the dorsal vein complex. In both groups, nerve-sparing techniques were applied when indicated. A 19F Blake drain was placed at the end of the case through the right lateral-most port.
For the radical nephrectomy, patients were placed in the flank position, and peritoneal access was gained via the open Hassan technique. In addition, two 12-mm assistant ports and two 8-mm robotic ports were placed. The hilar vessels were typically controlled with the Endo GIA stapler with a vascular load. Specimen extraction was usually made through a lower quadrant Gibson incision.
For the prostatectomy patients, standard postoperative care generally consisted of one night in the hospital, with removal of the drain and discharge on postoperative day #1. Catheter removal with a void trial was performed 5 to 10 days postoperatively, and a pathology discussion with the surgeon typically occurred 3 to 5 weeks postoperatively. Information about any complications, emergency department or other physician office visits in the interim was always inquired about. For the nephrectomy patients, postoperative care generally consisted of 1 to 2 nights in the hospital. Diet was advanced immediately after surgery, and patients were discharged once they were ambulatory, had pain controlled, and vital signs were stable.
Operative and clinical data were prospectively collected as part of an ongoing surgical database and analyzed retrospectively for this analysis. Each patient's anticoagulation status was reviewed by a nurse during the preoperative evaluation, and the last dose of any form of anticoagulation was prospectively, electronically documented. Beginning November 2009, the urology resident also documented preoperative anticoagulation status, as well as planned antiplatelet and anticoagulation therapy after the operation, in the inpatient progress notes.
The primary outcome of interest was the rate of transfusion and number of units of transfused packed red blood cells. Secondary outcomes included the operative time, estimated blood loss, need for platelet transfusions, length of hospital stay, frequency of reoperation for bleeding, and readmission for any reason. Operative time was defined as the time from the initial incision to the placement of the patient back in the supine position.
Baseline clinical characteristics, as well as operative and clinical outcomes, were compared between aspirin and preaspirin cohorts separately for each surgery type (ie, prostatectomy or nephrectomy). Categorical variables were summarized using counts and percents, and groups were compared using chi-square or Fisher exact tests. Continuous variables were reported as median with interquartile ranges (25th–75th percentiles). If not skewed, they were reported as mean with standard deviation. Groups were then compared using Kruskall-Wallis tests (for medians) or two-sample t tests (for means).
We identified 95 patients who met the inclusion criteria for this study and underwent robot-assisted prostatectomy; there were 51 patients in the aspirin cohort and 44 in the preaspirin cohort.
Baseline characteristics for the prostatectomy patients are presented in Table 1. There were no statistically significant differences in age, body mass index (BMI), American Society of anesthesiologists (ASA) score, prostate-specific antigen (PSA) value, or highest Gleason score between the two groups. There was a statistically significant difference in prostate volume, with a median volume 40 cc in the preaspirin cohort vs 35 cc in the aspirin cohort.
Procedural characteristics for the prostatectomy patients are listed in Table 2. No patient in either cohort received a blood transfusion or platelet transfusion. Operative time (182 vs 174 min, P=0.19), median blood loss (175 vs 100 mL, P=0.12), and length of hospital stay (1 vs 1 day, P=0.08) were similar between the preaspirin cohort and aspirin cohort, respectively. Four patients were readmitted in the 30 days after surgery for any reason: three patients in the preaspirin cohort (for a pulmonary embolus, hematuria, and a urinary tract infection) and one patient in the aspirin cohort (for an ileus). No patients in either cohort had a myocardial infarction or stroke.
There were 26 patients who underwent robot-assisted nephrectomy who met the inclusion criteria for this analysis; 12 preaspirin patients and 14 aspirin patients.
Baseline characteristics of the study population are presented in Table 3. There were no statistically significant differences in BMI or mass size between the two cohorts; however, there were statistically significant differences in median age and ASA score.
Procedural characteristics are listed in Table 4. As in the prostate cohort, no nephrectomy patient in either cohort received a blood transfusion or platelet transfusion. There were no significant differences in median blood loss (65 vs 50 mL, P=0.96), median operative time (176 vs 140 min, P=0.14), nor median hospital stay (2 vs 2 days, P=0.74) in the preaspirin and aspirin cohorts, respectively. Two patients were readmitted for any reason, both in the preasprin cohort: One patient was readmitted for renal failure and the other for an incarcerated incisional hernia. Two patients, both in the preaspirin cohort, had a thrombotic event: One had a symptomatic pulmonary embolus and a deep venous thombosis (DVT) developed in one patient. There were no such events in the aspirin cohort.
Although median blood loss volume was similar, the frequency of clinically significant blood loss was also examined. Although what constitutes clinically significant blood loss is poorly defined, we chose to retrospectively define clinically significant blood loss as greater than 500 mL. In the prostatectomy group, the overall frequency was 8.4%; 11.4% in the preaspirin cohort vs 5.9% in the aspirin cohort. For the nephrectomy group, the overall frequency was 11.5%; 16.7% in the preaspirin cohort vs 7.1% in the aspirin cohort.
This is the first evaluation of the safety of aspirin during radical prostatectomy and radical nephrectomy to our knowledge; all operations in this study were robot-assisted. The most significant finding of this study was that there was no evidence for an increase in bleeding, or surrogates of bleeding, when aspirin was continued, whether these were defined as either mean blood loss, blood loss >500 mL, need for transfusion, operative time, length of hospital stay, or need for readmission.
In 2005, Burger and associates1 performed an analysis of the risk and benefit of continuing low-dose aspirin throughout the perioperative period, weighing the potential reduction in cardiovascular risks vs a potential increase in bleeding. Despite the importance of this issue, there have been no studies—randomized, observational or retrospective—comparing the cardiovascular risks of preprocedural aspirin withdrawal directly against aspirin continuation in urologic surgery. Current practices in urology regarding perioperative aspirin vary depending on the type of surgical procedure and its associated risk of bleeding. With the increasing popularity of minimally invasive surgery, maintenance of aspirin during robot-assisted surgery may be safe but has not been investigated.
Three retrospective studies examined a consecutive series of patients with an acute coronary syndrome and the impact of aspirin withdrawal preceding the event. The incidence of myocardial infarction shortly after aspirin withdrawal ranged from 2.3% to 10.2%.1 Given the number of patients chronically receiving aspirin, the number of procedures performed each year before which aspirin is discontinued and the number of perioperative thrombotic events, the number of such events that might be prevented by continuing aspirin could be large. The same group attempted to evaluate the periprocedural bleeding risks of a variety of surgeries in patients who were on and off aspirin. They found 41 studies, which included 49,590 patients. Their meta-analysis concluded that aspirin multiplied the baseline bleeding rate by a factor of 1.5.1 The risk and consequences of bleeding, however, are undoubtedly related to the type of surgical procedure, surgical approach, and skill of the surgeon.
In addition to the cardioprotective effect of aspirin, a number of investigators have examined aspirin for its protective effect in a variety of malignancies. Rothwell and colleagues4 found that daily aspirin reduced deaths from several common cancers. Eight trials with 25,570 patients were reviewed, and the authors determined that aspirin reduced death from cancer (odds ratio [OR] 0.79, P=0.003). The 20-year risk of cancer death remained lower in the aspirin groups than in the control groups (all solid cancers, hazard ratio [HR] 0.80, P<0.0001 and gastrointestinal cancers, HR 0.65, P<0.0001).4
Aspirin use has also been reported for prostate cancer risk. Salinas and coworkers2 performed a population based case control study revealing a 21% reduction in the risk of prostate cancer among current users of aspirin/nonsteroidal anti-inflammatory drugs compared with nonusers.2 Mahmud and colleagues5 performed a meta-analysis of 10 case control and 14 cohort studies with a total of 24,230 prostate cancer cases. The effect of aspirin use on total prostate cancer had a pooled OR of 0.83, but the author noted that the studies were limited and concluded that the protective effect of aspirin against prostate cancer is suggestive but not conclusive.
Another potential benefit from the administration of aspirin perioperatively is a possible reduction in venous thromboembolism (VTE). Currently, there are no standard recommendations for pharmacologic DVT prophylaxis for urologic laparoscopic procedures. In 2008, the American Urologic Association assembled a panel to create best practice guidelines for the prevention of DVT in patients who were undergoing urologic surgery. There was a paucity of prospective data, however, that examined the issue in patients undergoing laparoscopic urologic procedures, and the panel recommended only intermittent pneumatic compression devices while acknowledging that high-risk groups may need additional pharmacologic prophylaxis. One multicenter study revealed that the rate of symptomatic VTE was 0.5% among 5951 patients undergoing laparoscopic radical prostatectomy.6 In another study, the incidence of pulmonary thromboembolism was 0.2% in 482 patients undergoing laparoscopic nephrectomy.7 Although the incidence of VTE is quite low, the large number of such cases performed each year suggests that VTE after urologic surgery likely results in significant morbidity and mortality, and complications might be prevented by the administration of aspirin.
Aspirin was shown to have a protective effect against VTE in a number of studies. In the Pulmonary Embolism Prevention trial, 13,356 patients undergoing hip fracture surgery or elective arthroplasty were randomized to 160 mg aspirin or placebo, and there were statistically significant 29% and 43% reductions in the relative risk of symptomatic DVT and pulmonary embolism, respectively.8 Although aspirin may not be as protective as warfarin, unfractionated or low molecular weight heparin in this setting, it may be safer, its oral administration makes it easier to administer, it is less expensive, and surgeons would undoubtedly be less reluctant to operate on patients taking aspirin than those taking anticoagulants.
There are several limitations to this study. All cases were performed by a single, experienced surgeon. Whether these results would be similar to those of a general population of urologic laparoscopic surgeons is unknown. In addition, the operations performed without aspirin were before those performed on an aspirin group. Therefore, the aspirin patients were operated on farther along the “learning curve” with robot-assisted surgery, which might explain why operative times were shorter for the aspirin group. Nonetheless, the risk of bleeding on aspirin was very low. Both study populations (prostatectomy and nephrectomy) were small; it is possible that a difference in bleeding might have emerged had many more patients been treated, even though no trends were seen. In fact, the trends went the other way, favoring the aspirin group. The power of this study to detect an increase in bleeding when total blood loss was analyzed as a continuous variable was much more than the power to detect any increase in clinical events that might have been related to aspirin. These data should increase the comfort of performing these operations in patients receiving aspirin and lead to larger, appropriately sized trials of perioperative aspirin among patients undergoing urologic and other types of surgery.
Perioperative aspirin appears to be safe in patients who are undergoing robot-assisted radical prostatectomy and robot-assisted radical nephrectomy. The risk of cardiovascular complications resulting from stopping aspirin may exceed the risk of perioperative bleeding and associated complications.
来源： JOURNAL OF ENDOUROLOGY