Swimming-Induced Pulmonary Edema: Pathophysiology and Risk Reduction With Sildenafil.

BACKGROUND: Swimming-induced pulmonary edema (SIPE) occurs during swimming or scuba diving, often in young individuals with no predisposing conditions, and its pathophysiology is poorly understood. This study tested the hypothesis that pulmonary artery and pulmonary artery wedge pressures are higher in SIPE-susceptible individuals during submerged exercise than in the general population and are reduced by sildenafil. METHODS AND RESULTS: Ten study subjects with a history of SIPE (mean age, 41.6 years) and 20 control subjects (mean age, 36.2 years) were instrumented with radial artery and pulmonary artery catheters and performed moderate cycle ergometer exercise for 6 to 7 minutes while submersed in 20°C water. SIPE-susceptible subjects repeated the exercise 150 minutes after oral administration of 50 mg sildenafil. Work rate and mean arterial pressure during exercise were similar in controls and SIPE-susceptible subjects. Average o2 and cardiac output in controls and SIPE-susceptible subjects were: o2 2.42 L·min(-1) versus 1.95 L·min(-1), P=0.2; and cardiac output 17.9 L·min(-1) versus 13.8 L·min(-1), P=0.01. Accounting for differences in cardiac output between groups, mean pulmonary artery pressure at cardiac output=13.8 L·min(-1) was 22.5 mm Hg in controls versus 34.0 mm Hg in SIPE-susceptible subjects (P=0.004), and the corresponding pulmonary artery wedge pressure was 11.0 mm Hg versus 18.8 mm Hg (P=0.028). After sildenafil, there were no statistically significant differences in mean pulmonary artery pressure or pulmonary artery wedge pressure between SIPE-susceptible subjects and controls. CONCLUSIONS: These observations confirm that SIPE is a form of hemodynamic pulmonary edema. The reduction in pulmonary vascular pressures after sildenafil with no adverse effect on exercise hemodynamics suggests that it may be useful in SIPE prevention. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00815646.

Marriage and mortality after noncardiac surgery.

BACKGROUND: Marriage is linked to substantial societal and economic benefits, and it has been associated with improved outcomes following acute illness. However, it is not known if being married confers benefit to patients undergoing noncardiac surgical procedures. MATERIALS AND METHODS: Patients undergoing any noncardiac surgical procedure were included over a period of 19 months. All-cause mortality at 2 years was determined by linking patient records to the National Death Index. Risk adjustment was performed using Cox modeling and the Cleveland Clinic risk stratification index. RESULTS: Of the 11,588 patients included, 7830 (68.0%) were married at the time of surgery. There was a significant interaction between sex and marital status (P = 0.03), so the remainder of the analysis was performed separately by sex. Among men, not being married was associated with significantly worse survival (hazard ratio [HR]: 1.31, 95% confidence interval [CI]: 1.06, 1.63), whereas among women, there was no significant association between marital status and survival (HR: 0.94, 95% CI: 0.77, 1.15). Furthermore, divorced men (HR: 1.76, 95% CI: 1.25, 2.51) and never married men (HR: 1.53, 95% CI: 1.14, 2.05) had significantly worse survival than married men, whereas there was no significant difference between widowed men and married men, nor when comparing widowed, divorced, or never married women to married women. CONCLUSIONS: Among a diverse group of surgical patients, being married at the time of surgery is associated with significantly improved survival only among men. Focused efforts to improve social support for unmarried male patients may improve outcomes.

Platelet Counts, Acute Kidney Injury, and Mortality after Coronary Artery Bypass Grafting Surgery.

BACKGROUND: Cardiac surgery requiring cardiopulmonary bypass is associated with platelet activation. Because platelets are increasingly recognized as important effectors of ischemia and end-organ inflammatory injury, the authors explored whether postoperative nadir platelet counts are associated with acute kidney injury (AKI) and mortality after coronary artery bypass grafting (CABG) surgery. METHODS: The authors evaluated 4,217 adult patients who underwent CABG surgery. Postoperative nadir platelet counts were defined as the lowest in-hospital values and were used as a continuous predictor of postoperative AKI and mortality. Nadir values in the lowest 10th percentile were also used as a categorical predictor. Multivariable logistic regression and Cox proportional hazard models examined the association between postoperative platelet counts, postoperative AKI, and mortality. RESULTS: The median postoperative nadir platelet count was 121 × 10/l. The incidence of postoperative AKI was 54%, including 9.5% (215 patients) and 3.4% (76 patients) who experienced stages II and III AKI, respectively. For every 30 × 10/l decrease in platelet counts, the risk for postoperative AKI increased by 14% (adjusted odds ratio, 1.14; 95% CI, 1.09 to 1.20; P < 0.0001). Patients with platelet counts in the lowest 10th percentile were three times more likely to progress to a higher severity of postoperative AKI (adjusted proportional odds ratio, 3.04; 95% CI, 2.26 to 4.07; P < 0.0001) and had associated increased risk for mortality immediately after surgery (adjusted hazard ratio, 5.46; 95% CI, 3.79 to 7.89; P < 0.0001). CONCLUSION: The authors found a significant association between postoperative nadir platelet counts and AKI and short-term mortality after CABG surgery.

Discordance in Grading Methods of Aortic Stenosis by Pre-Cardiopulmonary Bypass Transesophageal Echocardiography.

BACKGROUND: Current guidelines define severe aortic valve stenosis (AS) as an aortic valve area (AVA) ≤1.0 cm by the continuity equation and mean gradient (ΔPm) ≥ 40 mm Hg. However, these measurements can be discordant when classifying AS severity. Approximately one-third of patients with normal ejection fraction and severe AS by AVA have nonsevere AS by ΔPm when measured by preoperative transthoracic echocardiography (TTE). Given the use of positive pressure ventilation and general anesthesia in the pre-cardiopulmonary bypass (pre-CPB) period, we hypothesized that discordance between ΔPm and AVA during pre-CPB transesophageal echocardiography (TEE) would be higher than previously reported by TTE. METHODS: We retrospectively examined pre-CPB TEE data for patients who had aortic valve replacement, with or without coronary artery bypass grafting, from 2000 to 2012. Patients were excluded if they had ejection fraction <55%, emergency surgery, repeat sternotomy, moderate or severe mitral regurgitation, or severe aortic regurgitation. Only patients with both pre-CPB AVA and ΔPm measurements were included. Patients were grouped according to severity (mild, moderate, and severe) by AVA or ΔPm. Discordance was defined as disagreement between severities based on either parameter. RESULTS: A total of 277 patients met inclusion criteria. There were 227 patients with AVA ≤ 1.0 cm. The proportion of these patients with a ΔPm < 40 mm Hg was 54% (95% confidence interval, 47%-61%). The rate of discordance was significantly higher than the rate (37%; P < 0.001) found in previously reported analyses using TTE. Of the patients with a ΔPm ≥ 40 mm Hg, only 8% (n = 9/113) had a discordant AVA. In contrast, of the patients with ΔPm < 40 mm Hg, 80% (n = 131/164) had a discordant AVA. CONCLUSIONS: We confirmed our hypothesis that grading AS by ΔPm and AVA during pre-CPB TEE exhibits higher discordance than reported for TTE by others. It remains unclear whether these discrepancies reflect the effect of general anesthesia, imaging modality (TTE versus TEE) differences, inaccuracies in AS grading cutoffs when applied to pre-CPB TEE, or selection bias of the surgical population.

Baseline Pulse Pressure, Acute Kidney Injury, and Mortality After Noncardiac Surgery.

BACKGROUND: Increased pulse pressure (PP) is an important independent predictor of cardiovascular outcome and acute kidney injury (AKI) after cardiac surgery. The objective of this study was to determine whether elevated baseline PP is associated with postoperative AKI and 30-day mortality after noncardiac surgery. METHODS: We evaluated 9125 adult patients who underwent noncardiac surgery at Duke University Medical Center between January 2006 and December 2009. Baseline arterial blood pressure was defined as the mean of the first 5 measurements recorded by the automated record keeping system before inducing anesthesia. Multivariable logistic regression analysis was performed to determine whether baseline PP adjusted for other perioperative risk factors was independently associated with postoperative AKI and 30-day mortality. RESULTS: Of the 9125 patients, the baseline PP was <40 mm Hg in 1426 (15.6%), 40-80 mm Hg in 6926 (75.9%), and >80 mm Hg in 773 (8.5%) patients. The incidence of AKI was 19.8%, which included 8.4% (151 patients) and 4.2% (76 patients) who experienced stage II and III AKI, respectively. In the risk-adjusted model for postoperative AKI, elevated baseline PP was associated with higher odds for postoperative AKI (adjusted odds ratio [OR] for every 20 mm Hg increase in PP, 1.17; 95% confidence interval [CI], 1.10-1.25; P < .0001). Also elevated baseline preoperative PP was significantly associated with mild (stage I; OR, 1.19; 95% CI, 1.11-1.27; P < .0001), but not with more advanced stages of postoperative AKI or with an incremental risk for 30-day mortality. CONCLUSIONS: We found a significant association between elevated baseline PP and postoperative AKI in patients who underwent noncardiac surgery. However, elevated PP was not significantly associated with more advanced stages of postoperative AKI or 30-day mortality in these patients.

Intraoperative Magnesium Administration Does Not Reduce Postoperative Atrial Fibrillation After Cardiac Surgery.

BACKGROUND: Hypomagnesemia has been associated with an increased risk of postoperative atrial fibrillation (POAF). Although previous studies have suggested a beneficial effect of magnesium (Mg) therapy, almost all of these are limited by small sample size and relatively low Mg dose. We hypothesized that high-dose Mg decreases the occurrence of new-onset POAF, and we tested this hypothesis by using data from a prospective trial that assessed the effect of Mg on cognitive outcomes in patients undergoing cardiac surgery. METHODS: A total of 389 patients undergoing cardiac surgery were enrolled in this double-blind, placebo-controlled trial. Subjects were randomized to receive Mg as a 50-mg/kg bolus immediately after induction of anesthesia followed by another 50 mg/kg as an infusion given over 3 hours (total dose, 100 mg/kg) or placebo. We tested the effect of Mg therapy on POAF with logistic regression, adjusting for the risk of atrial fibrillation (AF) by using the Multicenter Study of Perioperative Ischemia risk index for Atrial Fibrillation after Cardiac Surgery. RESULTS: Among the 363 patients analyzed, after we excluded patients with chronic or acute preoperative AF (placebo: n = 177; Mg: n = 186), the incidence of new-onset POAF was 42.5% (95% confidence interval [CI], 35%-50%) in the Mg group compared with 37.9% (95% CI, 31%-45%) in the placebo group (P = 0.40). The 95% CI for this absolute risk difference of 4.6% is -5.5% to 14.7%. The time to onset of POAF also was identical between the groups, and no significant effect of Mg was found in logistic regression analysis after we adjusted for AF risk (odds ratio, 1.09; 95% CI, 0.69-1.72; P = 0.73). CONCLUSIONS: High-dose intraoperative Mg therapy did not decrease the incidence of new-onset POAF after cardiac surgery.

Apolipoprotein epsilon 4 genotype is associated with less improvement in cognitive function five years after cardiac surgery: a retrospective cohort study.

PURPOSE: Cognitive performance after cardiac surgery can be impaired, and genetic risk factors have previously been suggested. When compared with other isoforms of the gene, the apolipoprotein epsilon 4 (APOE4) allele is associated with worse outcomes in many neurologic disorders. We hypothesized that the APOE4 allele is associated with less favourable cognitive function five years after surgery. METHODS: Caucasian patients enrolled in previously reported prospective cognitive trials in both cardiac and non-cardiac surgery participated in this retrospective cohort study. Neuropsychological function was assessed at baseline and five years postoperatively. The relationship between change in cognitive index score and APOE was evaluated using multivariable linear regression. An additive genetic model toward the epsilon 4 allele was applied with adjustment for baseline cognition, years of education, age, presence of diabetes in both cohorts, and presence of coronary artery disease in the non-cardiac surgery cohort. RESULTS: A total of 357 patients were included in this study. In the cardiac surgery group (n = 233), baseline cognitive index (P < 0.001), years of education (P = 0.04), age at time of surgery (P < 0.001), and the APOE4 allele (P = 0.009), were associated with a five-year change in cognitive index. Patients carrying the APOE4 allele showed less improvement in cognitive index scores five years after cardiac surgery compared with patients without the APOE4 allele. In the non-cardiac surgery (n = 124) group, no association was found between APOE4 allele status and change in cognitive index. CONCLUSION: We report an association between APOE4 and neurocognitive function five years following cardiac surgery. Preoperative identification of patients with the APOE4 genotype may improve stratification of cardiac surgery patients at risk for a less favourable cognitive trajectory.

Cumulative duration of "triple low" state of low blood pressure, low bispectral index, and low minimum alveolar concentration of volatile anesthesia is not associated with increased mortality.

BACKGROUND: Mortality after noncardiac surgery has been associated with the "triple low state," a combination of low mean arterial blood pressure (<75 mmHg), low bispectral index (<45), and low minimum alveolar concentration of volatile anesthesia (<0.70). The authors set out to determine whether duration of a triple low state and aggregate risk associated with individual diagnostic and procedure codes are independently associated with perioperative and intermediate-term mortality. METHODS: The authors studied 16,263 patients (53 ± 16 yr) who underwent noncardiac surgery at Duke University Medical Center between January 2006 and December 2009. Multivariable logistic and Cox regression analyses were used to determine whether perioperative factors were independently associated with perioperative and intermediate-term all-cause mortality. RESULTS: The 30-day mortality rate was 0.8%. There were statistically significant associations between 30-day mortality and various perioperative risk factors including age, American Society of Anesthesiologists Physical Status, emergency surgery, higher Cleveland Clinic Risk Index score, and year of surgery. Cumulative duration of triple low state was not associated with 30-day mortality (multivariable odds ratio, 0.99; 95% CI, 0.92 to 1.07). The clinical risk factors for 30-day mortality remained predictors of intermediate-term mortality, whereas cumulative duration of triple low was not associated with intermediate-term mortality (multivariable hazard ratio, 0.98; 95% CI, 0.97 to 1.01). The multivariable logistic regression (c-index = 0.932) and Cox regression (c-index = 0.860) models showed excellent discriminative abilities. CONCLUSION: The authors found no association between cumulative duration of triple low state and perioperative or intermediate-term mortality in noncardiac surgery patients.

A prospective comparison of a noninvasive cardiac output monitor versus esophageal Doppler monitor for goal-directed fluid therapy in colorectal surgery patients.

BACKGROUND: Goal-directed fluid therapy (GDFT) is associated with improved outcomes after surgery. The esophageal Doppler monitor (EDM) is widely used, but has several limitations. The NICOM, a completely noninvasive cardiac output monitor (Cheetah Medical), may be appropriate for guiding GDFT. No prospective studies have compared the NICOM and the EDM. We hypothesized that the NICOM is not significantly different from the EDM for monitoring during GDFT. METHODS: One hundred adult patients undergoing elective colorectal surgery participated in this study. Patients in phase I (n = 50) had intraoperative GDFT guided by the EDM while the NICOM was connected, and patients in phase II (n = 50) had intraoperative GDFT guided by the NICOM while the EDM was connected. Each patient's stroke volume was optimized using 250-mL colloid boluses. Agreement between the monitors was assessed, and patient outcomes (postoperative pain, nausea, and return of bowel function), complications (renal, pulmonary, infectious, and wound complications), and length of hospital stay (LOS) were compared. RESULTS: Using a 10% increase in stroke volume after fluid challenge, agreement between monitors was 60% at 5 minutes, 61% at 10 minutes, and 66% at 15 minutes, with no significant systematic disagreement (McNemar P > 0.05) at any time point. The EDM had significantly more missing data than the NICOM. No clinically significant differences were found in total LOS or other outcomes. The mean LOS was 6.56 ± 4.32 days in phase I and 6.07 ± 2.85 days in phase II, and 95% confidence limits for the difference were -0.96 to +1.95 days (P = 0.5016). CONCLUSIONS: The NICOM performs similarly to the EDM in guiding GDFT, with no clinically significant differences in outcomes, and offers increased ease of use as well as fewer missing data points. The NICOM may be a viable alternative monitor to guide GDFT.

Reduced length of hospital stay in colorectal surgery after implementation of an enhanced recovery protocol.

BACKGROUND: Enhanced recovery after surgery (ERAS) is a multimodal approach to perioperative care that combines a range of interventions to enable early mobilization and feeding after surgery. We investigated the feasibility, clinical effectiveness, and cost savings of an ERAS program at a major U. S. teaching hospital. METHODS: Data were collected from consecutive patients undergoing open or laparoscopic colorectal surgery during 2 time periods, before and after implementation of an ERAS protocol. Data collected included patient demographics, operative, and perioperative surgical and anesthesia data, need for analgesics, complications, inpatient medical costs, and 30-day readmission rates. RESULTS: There were 99 patients in the traditional care group, and 142 in the ERAS group. The median length of stay (LOS) was 5 days in the ERAS group compared with 7 days in the traditional group (P < 0.001). The reduction in LOS was significant for both open procedures (median 6 vs 7 days, P = 0.01), and laparoscopic procedures (4 vs 6 days, P < 0.0001). ERAS patients had fewer urinary tract infections (13% vs 24%, P = 0.03). Readmission rates were lower in ERAS patients (9.8% vs 20.2%, P = 0.02). DISCUSSION: Implementation of an enhanced recovery protocol for colorectal surgery at a tertiary medical center was associated with a significantly reduced LOS and incidence of urinary tract infection. This is consistent with that of other studies in the literature and suggests that enhanced recovery programs could be implemented successfully and should be considered in U.S. hospitals.

Intraoperative magnesium administration does not improve neurocognitive function after cardiac surgery.

BACKGROUND AND PURPOSE: Neurocognitive decline occurs frequently after cardiac surgery and persists in a significant number of patients. Magnesium is thought to provide neuroprotection by preservation of cellular energy metabolism, blockade of the N-methyl-D-aspartate receptor, diminution of the inflammatory response, and inhibition of platelet activation. We therefore hypothesized that intraoperative magnesium administration would decrease postoperative cognitive impairment. METHODS: After approval by the Duke University Health System Institutional Review Board, 389 patients undergoing cardiac surgery were enrolled in this prospective, randomized, double-blind, placebo-controlled clinical trial. Subjects were randomized to receive magnesium as a 50 mg/kg bolus followed by another 50 mg/kg infusion for 3 hours or placebo bolus and infusion. Cognitive function was assessed preoperatively and again at 6 weeks postoperatively using a standardized test battery. Mean CD11b fluorescence and percentage of platelets expressing CD62P, which are markers of leukocyte and platelet activation, respectively, were assessed by flow cytometry as a secondary outcome. The effect of magnesium on postoperative cognition was tested using multivariable regression modeling, adjusting for age, years of education, baseline cognition, sex, race, and weight. RESULTS: Among the 389 allocated subjects (magnesium: n=198; placebo: n=191), the incidence of cognitive deficit in the magnesium group was 44.4% compared with 44.9% in the placebo group (P=0.93). The cognitive change score and platelet and leukocyte activation were also not different between the groups. Multivariable analysis revealed a marginal interaction between treatment group and weight such that heavier subjects receiving magnesium were less likely to have cognitive deficit (P=0.06). CONCLUSIONS: Magnesium administered intravenously during cardiac surgery does not reduce postoperative cognitive dysfunction. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041392.

Thrombomodulin gene variants are associated with increased mortality after coronary artery bypass surgery in replicated analyses.

BACKGROUND: We tested the hypothesis that genetic variation in thrombotic and inflammatory pathways is independently associated with long-term mortality after coronary artery bypass graft (CABG) surgery. METHODS AND RESULTS: Two separate cohorts of patients undergoing CABG surgery at a single institution were examined, and all-cause mortality between 30 days and 5 years after the index CABG was ascertained from the National Death Index. In a discovery cohort of 1018 patients, a panel of 90 single-nucleotide polymorphisms (SNPs) in 49 candidate genes was tested with Cox proportional hazard models to identify clinical and genomic multivariate predictors of incident death. After adjustment for multiple comparisons and clinical predictors of mortality, the homozygote minor allele of a common variant in the thrombomodulin (THBD) gene (rs1042579) was independently associated with significantly increased risk of all-cause mortality (hazard ratio, 2.26; 95% CI, 1.31 to 3.92; P=0.003). Six tag SNPs in the THBD gene, 1 of which (rs3176123) in complete linkage disequilibrium with rs1042579, were then assessed in an independent validation cohort of 930 patients. After multivariate adjustment for the clinical predictors identified in the discovery cohort and multiple testing, the homozygote minor allele of rs3176123 independently predicted all-cause mortality (hazard ratio, 3.6; 95% CI, 1.67 to 7.78; P=0.001). CONCLUSIONS: In 2 independent cardiac surgery cohorts, linked common allelic variants in the THBD gene are independently associated with increased long-term mortality risk after CABG and significantly improve the classification ability of traditional postoperative mortality prediction models.

Impact of transfusion of autologous 7- versus 42-day-old AS-3 red blood cells on tissue oxygenation and the microcirculation in healthy volunteers.

BACKGROUND: Stored red blood cells (RBCs) accumulate biochemical and biophysical changes. Maximum storage duration is based on acceptable in vitro characteristics and 24-hour survival, but not RBC function. Relatively little is known about the impact of RBC storage duration on oxygenation and the microcirculation. STUDY DESIGN AND METHODS: Eight healthy subjects donated a double RBC apheresis, which were prestorage leukoreduced and processed in AS-3. Subjects were transfused 1 unit of RBCs at 7 and 42 days after blood collection. Measurements of percentage of tissue oxygenation in the thenar eminence muscle (StO2) and brain (SctO2) were recorded with Food and Drug Administration-cleared noninvasive devices. Sublingual microvascular blood flow (microcirculatory flow index [MFI]) was quantified before and after RBC transfusion using a video microscope. Raw electronic data for all measurements were analyzed by a blinded observer at a core laboratory. RESULTS: The only pre- versus posttransfusion change observed in measurements of SctO2, StO2, or MFI was a very small increase in SctO2, from 70.4 to 71.8 (means, p=0.032) at 7 days. There was no significant difference in the amount of pre-post change at 7 days versus 42 days for any of the measures. CONCLUSION: Transfusion of 1 unit of 42-day-stored RBCs to healthy subjects has no overt detrimental effect on tissue oxygenation or the microcirculation assessed by clinically available monitors.

Obstructive sleep apnea and incidence of postoperative delirium after elective knee replacement in the nondemented elderly.

BACKGROUND: Postoperative delirium, a common complication in the elderly, can occur following any type of surgery and is associated with increased morbidity and mortality; it may also be associated with subsequent cognitive problems. Effective therapy for postoperative delirium remains elusive because the causative factors of delirium are likely multiple and varied. METHODS: Patients 65 yr or older undergoing elective knee arthroplasty were prospectively evaluated for postoperative Diagnostic and Statistical Manual of Mental Disorders-IV delirium. Exclusion criteria included dementia, mini-mental state exam score less than 24, delirium, clinically significant central nervous system/neurologic disorder, current alcoholism, or any serious psychiatric disorder. Delirium was assessed on postoperative days 2 and 3 using standardized scales. Patients' preexisting medical conditions were obtained from medical charts. The occurrence of obstructive sleep apnea was confirmed by contacting patients to check their polysomnography records. Data were analyzed using Pearson chi-square or Wilcoxon rank sum tests and multiple logistic regressions adjusted for effects of covariates. RESULTS: Of 106 enrolled patients, 27 (25%) developed postoperative delirium. Of the 15 patients with obstructive sleep apnea, eight (53%) experienced postoperative delirium, compared with 19 (20%) of the patients without obstructive sleep apnea (P = 0.0123, odds ratio: 4.3). Obstructive sleep apnea was the only statistically significant predictor of postoperative delirium in multivariate analyses. CONCLUSIONS: This is the first prospective study employing validated measures of delirium to identify an association between preexisting obstructive sleep apnea and postoperative delirium.

Vertebral insufficiency fractures as a cause of autonomic dysreflexia in a patient with chronic tetraplegia: A case report.

Context: Osteoporosis is a known complication in spinal cord injury patients and can result in an increased risk of fractures and associated morbidity. Bone demineralization is most common in long bones below the level of injury. The pathogenesis is complex and not fully understood.Findings: We present the case of a 65-year-old male with chronic spinal cord injury who was found to have multiple vertebral compression fractures causing autonomic dysreflexia and new onset spasticity.Conclusion/Clinical Relevance: This case illustrates the need for improved awareness, diagnosis, and prevention for this disease process.

The interdisciplinary management of coccydynia: A narrative review.

Pain that develops in the coccyx or surrounding tissues is known as coccydynia, which occurs as a result of many etiologies both traumatic and nontraumatic. Although coccydynia most commonly affects middle-aged women, it may be found in both sexes and in all age groups. The aim of this article is to provide an overview of the presentation, diagnostic imaging, and pathophysiology of coccydynia, and to comprehensively review the current treatment options. A review of publications from 1990 to 2020 using search words related to the treatment of coccydynia in PubMed and Google Scholar was completed. Level II evidence was found supporting stretching, manipulation, and extracorporeal shock wave therapy. There are no data from high-quality studies to support injection-based therapy including corticosteroids, prolotherapy, nerve blocks, and radiofrequency ablation, although there are small retrospective and prospective observational studies suggesting benefit. Level III evidence was found supporting coccygectomy for chronic/refractory coccydynia. There are no data from randomized controlled trials to support the use of neuromodulation (sacral burst and dorsal root ganglion stimulation), although there are case reports suggesting benefit. High-level, comparative studies are lacking to guide the treatment of coccydynia and should be a focus for future research studies.

The effect of aprotinin on outcome after coronary-artery bypass grafting.

BACKGROUND: Aprotinin has recently been associated with adverse outcomes in patients undergoing cardiac surgery. We reviewed our experience with this agent in patients undergoing cardiac surgery at Duke University Medical Center. METHODS: We retrieved data on 10,275 consecutive patients undergoing surgical coronary revascularization at Duke between January 1, 1996, and December 31, 2005. We fit data to a logistic-regression model predicting each patient's likelihood of receiving aprotinin on the basis of preoperative characteristics and to models predicting long-term survival (up to 10 years) and decline in renal function, as measured by increases in serum creatinine levels. RESULTS: A total of 1343 patients (13.2%) received aprotinin, 6776 patients (66.8%) received aminocaproic acid, and 2029 patients (20.0%) received no antifibrinolytic therapy. All patients underwent coronary-artery bypass grafting, and 1181 patients (11.5%) underwent combined coronary-artery bypass grafting and valve surgery. In the risk-adjusted model, survival was worse among patients treated with aprotinin, with a main-effects hazard ratio for death of 1.32 (95% confidence interval [CI], 1.12 to 1.55) for the comparison with patients receiving no antifibrinolytic therapy (P=0.003) and 1.27 (95% CI, 1.10 to 1.46) for the comparison with patients receiving aminocaproic acid (P=0.004). As compared with the use of aminocaproic acid or no antifibrinolytic agent, aprotinin use was also associated with a larger risk-adjusted increase in the serum creatinine level (P<0.001) but not with a greater risk-adjusted incidence of dialysis (P=0.56). CONCLUSIONS: Patients who received aprotinin had a higher mortality rate and larger increases in serum creatinine levels than those who received aminocaproic acid or no antifibrinolytic agent.

A comparison of the combination of aprepitant and dexamethasone versus the combination of ondansetron and dexamethasone for the prevention of postoperative nausea and vomiting in patients undergoing craniotomy.

BACKGROUND: Postoperative nausea and vomiting (PONV) occur commonly after craniotomy. In patients receiving prophylaxis with ondansetron and dexamethasone, vomiting occurred in 45% of patients at 48 hours. In addition to causing patient discomfort, the physical act of vomiting may increase intracranial pressure or cerebral intravascular pressure, jeopardizing hemostasis and cerebral perfusion. Aprepitant is a neurokin-1 receptor antagonist with a long duration of action and no sedative side effect. In a large multicenter study in patients undergoing abdominal surgery, aprepitant was significantly more effective than was ondansetron in preventing vomiting at 24 and 48 hours postoperatively. We hypothesized that the combination of aprepitant with dexamethasone will decrease the incidence of postoperative vomiting when compared with the combination of ondansetron and dexamethasone in patients undergoing craniotomy under general anesthesia. METHODS: Patients scheduled to undergo craniotomy under general anesthesia were enrolled in this prospective, double-blind, randomized study. Patients were randomized to receive oral aprepitant 40 mg (or matching placebo) 1 to 3 hours before induction of anesthesia or ondansetron 4 mg IV (or placebo) within 30 minutes of the end of surgery. All patients received dexamethasone 10 mg after induction of anesthesia. The anesthetic technique was standardized. Data were collected at regular intervals by blinded personnel for 48 hours after surgery. Statistical analysis was performed using Wilcoxon's ranked sum test and χ(2) test. P < 0.05 was considered statistically significant. RESULTS: One hundred four patients completed the study. The cumulative incidence of vomiting at 48 hours was 16% in the aprepitant group and 38% in the ondansetron group (P = 0.0149). The incidence of vomiting was also decreased in the aprepitant group at 2 hours (6% vs. 21%, P = 0.0419) and 24 hours (14% vs. 36%, P = 0.0124). From 0 to 48 hours, there was no difference between the aprepitant and ondansetron groups in the incidence of nausea (69% vs. 60%), nausea scores, need for rescue antiemetics (65% vs. 60%), complete response (no PONV and no rescue, 22% vs. 36%), or patient satisfaction with the management of PONV. CONCLUSION: The combination of aprepitant and dexamethasone was more effective than was the combination of ondansetron and dexamethasone for prophylaxis against postoperative vomiting in adult patients undergoing craniotomy under general anesthesia. However, there was no difference between the groups in the incidence or severity of nausea, need for rescue antiemetics, or in complete response between the groups.