YingXing Wu

Effect of hyperglycemia and continuous intravenous insulin infusions on outcomes of cardiac surgical procedures: the Portland Diabetic Project.

OBJECTIVE To describe the main findings of the Portland Diabetic Project, which elucidates the adverse relationship between hyperglycemia and outcomes of cardiac surgical procedures in patients with diabetes and delineates the protective effects of intravenous insulin therapy in reducing those adverse outcomes. RESULTS In this ongoing 17-year prospective, nonrandomized, interventional study of 4,864 patients with diabetes who underwent an open-heart surgical procedure, we investigated the effects of hyperglycemia, and its subsequent reduction by continuous intravenous insulin (CII) therapy, on in-hospital outcomes. Increasing blood glucose levels were found to be directly associated with increasing rates of death, deep sternal wound infections (DSWI), length of hospital stay (LOS), and hospital cost. In separate multivariate analyses, increasing hyperglycemia was found to be independently predictive of increasing mortality (P<0.0001), DSWI (P = 0.017), and LOS (P<0.002). Conversely, CII therapy, designed to achieve predetermined target blood glucose levels, independently reduced the risks of death and DSWI by 57% and 66%, respectively (P<0.0001 for both). Target blood glucose levels of less than 150 mg/dL and a 3-day postoperative duration of CII therapy are both important variables that determine the effect of the CII therapy on improved outcomes. Coronary artery bypass grafting-related mortality (2.5%) and DSWI rates (0.8%) in patients with diabetes were normalized to those of the nondiabetic population by the use of the Portland CII Protocol. CONCLUSION Perioperative hyperglycemia in patients undergoing a cardiac surgical procedure affects biochemical and physiologic functions, which, in turn, adversely alter mortality, LOS, and infection rates. The Portland CII Protocol is a cost-efficient method that effectively eliminates hyperglycemia and reduces postoperative morbidity and mortality in patients with diabetes undergoing an open-heart operation. CII protocols should be the standard care for glycometabolic control in all patients undergoing cardiac surgical procedures.

CLINICAL EFFECTS OF HYPERGLYCEMIA IN THE CARDIAC SURGERY POPULATION: THE PORTLAND DIABETIC PROJECT

OBJECTIVE To determine the outcome effects of hyperglycemia, and its pharmacologic reduction with continuous intravenous insulin infusions (CII) in the cardiac surgery patient population. METHODS The Portland Diabetic Project is a prospective, non-randomized, observational study of 5,510 consecutive diabetic cardiac surgery patients treated between January 1987 and November 2005. RESULTS This study was the first to reveal that hyperglycemia in the first 3 postoperative days is independently predictive of mortality (P<0.0001), deep sternal wound infection (P= 0.0001), and increased length of stay (P<0.002) in diabetic cardiac surgery patients. Conversely, CII, designed to achieve predetermined target glucose levels, was shown to independently reduce the risks of death and deep sternal wound infection by 60% and 77%, respectively (P<0.001 for both). Target glucose levels <150 mg/dL and a 3-day postoperative duration of CII therapy are both important variables that determine the impact of the CII therapy on improved outcomes. CONCLUSIONS Perioperative hyperglycemia in cardiac surgery patients adversely alters mortality, length of stay, and infection rates. Three days of CII eliminates the incrementally increased risks of these complications previously seen in diabetic patients.

Aprotinin Does Not Increase the Risk of Renal Failure in Cardiac Surgery Patients

Background— Aprotinin is frequently used in high-risk cardiac surgery patients to decrease bleeding complications and transfusions of packed red blood cells (PRBC). Transfusions of PRBC are known to directly increase the risk of new onset postoperative renal failure (ARF) in cardiac surgery patients. A recent highly publicized report implicated aprotinin as an independent causal factor for postoperative renal failure, but ignored the potential confounding affect of numerical PRBC data on ARF. We sought to investigate that claim with an analysis that included all perioperative risk factors for renal failure, including PRBC transfusion data. Methods and Results— Prospectively collected patient data from 12 centers contributing to the Merged Cardiac Registry, an international multicenter cardiac surgery database, operated on between January 2000 and February 2006 were retrospectively analyzed. A previously published risk model for ARF incorporating 12 variables was used to calculate a baseline ARF risk score for each patient in whom those variables were available (n=15 174). After adding transfused PRBC data 11 198 patients remained for risk-adjusted assessment of ARF in relation to aprotinin use. Risk-adjusted multivariable analyses were carried out with, and without, consideration of transfused PRBC. Aprotinin was used in 24.6% (2757/11 198). The overall incidence of ARF was 1.6% (180/11 198) and was higher in the aprotinin subset (2.6%, 72/2757 versus 1.3%, 108/8441; P<0.001). The incidence of ARF directly and significantly increased with increasing transfusions of PRBC (P<0.001). Risk-adjusted analysis without transfused PRBC in the model suggests that aprotinin significantly impacts ARF (P=0.008; OR=1.5). However, further risk adjustment with the addition of the highly significant transfused PRBC variable (P<0.0001; OR=1.23/transfused PRBC) to the model attenuates the purported independent affect of aprotinin (P=0.231) on ARF. Conclusions— The increase in renal failure seen in patients who were administered aprotinin was directly related to increased number of transfusions in that high-risk patient population. Aprotinin use does not independently increase the risk of renal failure in cardiac surgery patients.

Delayed umbilical cord clamping in premature neonates.

OBJECTIVE: Delayed umbilical cord clamping is reported to increase neonatal blood volume. We estimated the clinical outcomes in premature neonates who had delayed umbilical cord clamping compared with a similar group who had early umbilical cord clamping. METHODS: This was a before–after investigation comparing early umbilical cord clamping with delayed umbilical cord clamping (45 seconds) in two groups of singleton neonates, very low birth weight (VLBW) (401–1,500 g) and low birth weight (LBW) (greater than 1,500 g but less than 35 weeks gestation). Neonates were excluded from delayed umbilical cord clamping if they needed immediate major resuscitation. Primary outcomes were provision of delivery room resuscitation, hematocrit, red cell transfusions, and the principle Vermont Oxford Network outcomes. RESULTS: In VLBW neonates (77 delayed umbilical cord clamping, birth weight [mean±standard deviation] 1,099±266 g; 77 early umbilical cord clamping 1,058±289 g), delayed umbilical cord clamping was associated with less delivery room resuscitation, higher Apgar scores at 1 minute, and higher hematocrit. Delayed umbilical cord clamping was not associated with significant differences in the overall transfusion rate, peak bilirubin, any of the principle Vermont Oxford Network outcomes, or mortality. In LBW neonates (172 delayed umbilical cord clamping, birth weight [mean±standard deviation] 2,159±384 g; 172 early umbilical cord clamping 2,203±447 g), delayed umbilical cord clamping was associated with higher hematocrit and was not associated with a change in delivery room resuscitation or Apgar scores or with changes in the transfusion rate or peak bilirubin. Regression analysis showed increasing gestational age and birth weight and delayed umbilical cord clamping were the best predictors of higher hematocrit and less delivery room resuscitation. CONCLUSION: Delayed umbilical cord clamping can safely be performed in singleton premature neonates and is associated with a higher hematocrit, less delivery room resuscitation, and no significant changes in neonatal morbidities. LEVEL OF EVIDENCE: II

Long-term Results after Carpentier-Edwards Pericardial Aortic Valve Implantation, with Attention to the Impact of Age

BACKGROUND The purpose of this study was to determine long-term patient survival and valve durability for Carpentier-Edwards pericardial valves (Edwards Lifesciences) implanted in the aortic position, with specific attention to the impact of patient age. METHODS We performed a retrospective cohort study of 2168 patients who underwent implantation of a Carpentier-Edwards pericardial aortic valve between 1991 and 2008. The mean follow-up time was 4.5 years. Primary outcomes of interest were mortality and valve explantation. Survival curves and event-free curves were obtained with the Kaplan-Meier method and compared with the log-rank test. RESULTS Survival was 92% at 1 year, 73% at 5 years, 38% at 10 years, and 18% at 15 years. Although the mortality rate of younger patients was worse than in the general population, older patients had significantly better survival than their contemporaries. Age was the independent variable most significantly associated with explantation. There was an early hazard phase for patients between 21 and 49 years of age, such that the freedom from explantation was 89% at 3 years. By 10 years, the freedom from explantation was 58% for patients 21 to 49 years of age, compared with 68% for patients 50 to 64 years, 93% for patients 65 to 74 years, and 99% for patients 75 years of age and older. CONCLUSION We found good long-term survival and durability. Older patients had excellent freedom from explantation, whereas younger patients fared worse. As our population ages, this information becomes increasingly important. Assessing the durability of this pericardial aortic valve may aid in predicting the durability of the transcatheter aortic valves that share the same leaflets.

The Risks and Benefits of Reoperative Aortic Valve Replacement

BACKGROUND Many patients are advised to have mechanical aortic valve replacement (AVR) because their expected longevity exceeds that of tissue prostheses. This strategy may avoid the risks of reoperation but exposes patients to the risks of long-term anticoagulation therapy. Which risk is greater? METHODS We reviewed the records of 1213 consecutive, unselected AVR patients, 60% of whom had concomitant procedures, who were treated from 1994 through 2002. Of these patients, 887 were first-time AVR patients, and 326 underwent reoperation. Of the reoperation patients, 134 had previously undergone AVR (redo). We constructed a risk model from these 1213 cases to assess the factors that predicted mortality and to examine the extent to which reoperation affected outcome. RESULTS Multiple logistic regression analysis indicated that factors of reoperation and redo operation did not predict mortality. In fact, the mortality rate was 4.1% for all first AVR operations and 3.1% for all reoperation AVR ( P =.891). Significant predicting factors (with odds ratios) were reoperative dialysis (6.03), preoperative shock (3.68), New York Heart Association class IV (2.20), female sex (1.76), age (1.61), and cardiopulmonary bypass time (1.26). CONCLUSIONS In this series, the risk of reoperation AVR is comparable with the published risks of long-term warfarin sodium (Coumadin) administration after mechanical AVR. Any adult who requires AVR may be well advised to consider tissue prostheses.

A Primer on Using Shrinkage to Compare In-Hospital Mortality Between Centers

Outcomes of cardiothoracic surgery are usually compared among hospitals or physicians by reporting the frequency of in-hospital mortality. Although there is agreement that these frequencies should be adjusted for case mix, there remains uncertainty about the value of using a statistical model that represents hospitals as random effects as opposed to the conventional approach of fixed effects. For years, the Northern New England Cardiovascular Disease Study Group has compared in-hospital mortality after coronary artery bypass graft surgery among centers using a fixed effects approach. An alternative method using random effects has become increasingly popular, and is the method used by cardiothoracic surgery registries such as the Massachusetts Data Analysis Center. The purpose of this report is to provide a short background on fixed versus random effects modeling, describe the use of shrinkage estimators including empirical Bayes, and illustrate them using data from the Northern New England Cardiovascular Disease Study Group. We conclude that both are acceptable approaches to hospital profiling if done in combination with appropriate risk adjustment.

Permissive tolerance of the patent ductus arteriosus may increase the risk of Chronic Lung Disease

Correspondence: Joseph W Kaempf Pediatrix Medical Group, Providence St Vincent Medical Center, 9205 SW Barnes Road, Portland, OR 97225, USA Tel +1 503 216 7383 Email joseph_kaempf@pediatrix.com Purpose: Because early closure therapies of the patent ductus arteriosus (PDA) have not been shown to confer benefit to premature infants, the authors’ four neonatal intensive care units adopted a less aggressive PDA management protocol. Study design: A before–after investigation in infants with PDAs born 501–1500 g. Era 1 (January 2005 to December 2007) featured traditional management with indomethacin and/or surgical ligation used early to close PDAs; Era 2 (January 2008 to June 2009) featured fluid restriction and watchful waiting for PDA closure, limiting indomethacin or surgical ligation to only those infants with large PDAs needing significant respiratory support. Results: Era 2 infants (n = 129, mean ± standard deviation 27 ± 2 weeks) received less and later indomethacin and less Day 1–28 total fluids as compared to Era 1 infants (n = 240, mean ± standard deviation 27 ± 2 weeks). The Chronic Lung Disease (CLD) rate was higher in Era 2 (48% versus 34%, P , 0.01) as was the combined outcome of Death after Day 7 or CLD (57% versus 42%, P , 0.01). Multiple regression analysis showed Era 2 birth was a predictor of CLD. However, Poisson regression analysis determined the predictors of all seven major Vermont Oxford Network morbidities were earlier gestational age, lower birth weight, and male gender, not the era of birth. Significantly more infants were discharged home with PDAs in Era 2. Conclusion: Permissive tolerance of PDAs may increase the risk of CLD and Death after Day 7 or CLD but is not associated with significant changes in other Vermont Oxford Network morbidities.

Initial clinical trial of substernal epicardial echocardiography: SEEing a new window to the postoperative heart.

BACKGROUND Postoperative echocardiography windows are often of poor quality because of intervening air spaces around the heart and great vessels. We assessed the utility of a new commercially available adult chest drainage tube that has been modified with the addition of a sterile sleeve to accommodate the introduction of a nonsterile pediatric transesophageal echocardiography (TEE) probe. The TEE probe lies in a substernal epicardial position on the postoperative heart allowing one to perform substernal epicardial echocardiography (SEE). METHODS Informed consent was obtained from 21 consecutive adult cardiac operation patients. At the completion of the operation the SEE drainage tube was inserted through the rectus muscle and into the pericardium. After chest closure, all patients underwent a full echo examination using an Acuson pediatric biplane probe in the SEE position. Views obtained and ease of insertion were judged on a 1 to 10 (worst to best) scale. RESULTS Full SEE examinations were completed in an average of 12 minutes. Ease of probe entry and manipulation was excellent (ratings of 9.3 and 9.6, respectively). The quality of the anatomic images was also excellent. Substernal epicardial echocardiography tube positioning was integral to the orientation of the images obtained. There were no complications related to the placement of the SEE tubes or TEE probes. In 4 of 21 patients (19%) the SEE methodology was used serially in the intensive care unit to accurately assess ventricular function and filling during weaning of an intraaortic balloon and inotropic agents. CONCLUSIONS Substernal epicardial echocardiography is a safe and highly effective methodology for the serial echocardiographic assessment of the postoperative heart.

Using the National Death Index to Validate the Noninformative Censoring Assumption of Survival Estimation

BACKGROUND In survival analysis, a patient who is missing complete follow-up is included in the analysis as a censored observation. The analysis makes the assumption that the censoring is noninformative; that is, that a censored patient has the same risk of death as those who have complete follow-up. We tested this assumption in a large, long-term follow-up study. METHODS From 1986 through 2003, 14,495 patients underwent isolated coronary artery bypass grafting procedures. Of 13,963 eligible patients, 2312 were lost to follow-up. We obtained National Death Index data to complete our follow-up, and then compared survival between the original data and the complete National Death Index-augmented data. RESULTS The National Death Index data revealed 855 additional deaths and increased the total follow-up years from 86,810 to 102,157. Survival estimates and regression models did not differ between the original and National Death Index-augmented data. CONCLUSIONS Patients lost to follow-up might not differ with regard to survival from those with complete data. The requirement for 95% completeness is somewhat arbitrary. The quality and type of follow-up is more important than the percentage in time-related analyses.