Daniel J. Lex

Acute kidney injury is associated with higher morbidity and resource utilization in pediatric patients undergoing heart surgery.

BACKGROUND The RIFLE (risk, injury, failure, loss, and end-stage renal disease) classification system was developed to standardize the definition of acute kidney injury (AKI) in adults. We hypothesized that AKI was associated with increased mortality and morbidity. METHODS Acute kidney injury was defined as a decrease in the amount of estimated creatinine clearance based on pediatric-modified RIFLE (pRIFLE) criteria. Using propensity score analysis, 325 patients who had AKI were matched to 325 patients who did not have AKI from a database of 1,510 consecutive pediatric patients who underwent cardiac surgery between January 2004 and December 2008 at a single center. The association between AKI and outcome was analyzed after propensity score matching of perioperative variables. RESULTS Four hundred eighty-one patients (31.9%) had AKI according to the RIFLE categories. Of those 1,510, 173 (11.5%) reached pRIFLE criteria for risk; 26 (1.7%) reached the criteria for injury; and 282 (18.7%) reached the criteria for failure. Fifty-five patients (3.6%) died. The 2 matched groups were well balanced in terms of measured perioperative variables. Mortality rate was 5.2% in the AKI and 2.5% in the matched control group (p=0.09). Occurrence of low cardiac output syndrome (p=0.002), need for dialysis (p<0.001), and infection (p=0.03) were significantly higher, and duration of mechanical ventilation (p<0.001) and length of intensive care unit stay (p<0.001) were significantly longer compared with the matched control group. CONCLUSIONS Acute kidney injury was independently associated with an increased occurrence of postoperative complications but not with mortality after pediatric cardiac surgery.

A Comparison of the Systems for the Identification of Postoperative Acute Kidney Injury in Pediatric Cardiac Patients

BACKGROUND The pediatric-modified Risk, Injury, Failure and Loss, and End-Stage (pRIFLE) criteria and a different but conceptually similar system termed Acute Kidney Injury Network (AKIN) were created to standardize the definition of acute kidney injury (AKI) in children. Kidney Disease: Improving Global Outcomes (KDIGO) currently recommends a combination of AKIN and pRIFLE in AKI. This study aimed to compare the three classifications for predicting AKI in pediatric patients undergoing cardiac operations. METHODS We analyzed the prospectively collected data of 1,489 consecutive pediatric patients undergoing cardiac operations between January 2004 and December 2008. AKI presence and severity was assessed for each classification using the change in serum creatinine and estimated creatinine clearance levels calculated by the Schwartz equation. RESULTS AKI was present in 285 (20%), 481 (34%), and 409 (29%) patients according to the AKIN, pRIFLE, and KDIGO systems, respectively. The KDIGO classification categorized 121 patients (8%) who were placed in the AKIN 0 category, whereas the pRIFLE system categorized 74 (5%) in KDIGO 0 and 200 (14%) in AKIN 0 stages as having an AKI. The overall mortality rate was 3.9%. The KDIGO stage III (odds ratio [OR], 18.8; 95% confidence interval [CI], 9.6 to 36.6, p < 0.001), the AKIN stage III (OR, 38.3; 95% CI, 20.6 to 70.9, p < 0.001), and pRIFLE failure group (OR, 13.6, 95% CI, 7 to 26.3; p < 0.001) were associated with increased mortality. CONCLUSIONS The pRIFLE system was the most sensitive test in detecting AKI, and this was especially so in the infant age group and also in the early identification of AKI in low-risk patients. The AKIN system was more specific and detected mostly high-risk patients across all age groups. The KDIGO classification system fell between pRIFLE and AKIN in performance. All three had increasing severity of AKI associated with mortality.

Fluid Overload Is Associated With Higher Mortality and Morbidity in Pediatric Patients Undergoing Cardiac Surgery.

Objectives: Fluid overload after pediatric cardiac surgery is common and has been shown to increase both mortality and morbidity. This study explores the risk factors of early postoperative fluid overload and its relationship with adverse outcomes. Design: Secondary analysis of the prospectively collected data of children undergoing open-heart surgery between 2004 and 2008. Setting: Tertiary national cardiac center. Patients: One thousand five hundred twenty consecutive pediatric patients (<18 years old) were included in the analyses. Interventions: None. Measurements and Main Results: In the first 72 hours of the postoperative period, the daily fluid balance was calculated as milliliter per kilogram and the daily fluid overload was calculated as fluid balance (L)/weight (kg) × 100. The primary endpoint was in-hospital mortality; the secondary outcomes were low cardiac output syndrome and prolonged mechanical ventilation. One thousand three hundred and sixty-seven patients (89.9%) had a cumulative fluid overload below 5%; 120 patients (7.8%), between 5% and 10%; and 33 patients (2.1%), above 10%. After multivariable analysis, higher fluid overload on the day of the surgery was independently associated with mortality (adjusted odds ratio, 1.14; 95% CI, 1.008–1.303; p = 0.041) and low cardiac output syndrome (adjusted odds ratio, 1.21; 95% CI, 1.12–1.30; p = 0.001). Higher maximum serum creatinine levels (adjusted odds ratio, 1.01; 95% CI, 1.003–1.021; p = 0.009), maximum vasoactive-inotropic scores (adjusted odds ratio, 1.01; 95% CI, 1.005–1.029; p = 0.042), and higher blood loss on the day of the surgery (adjusted odds ratio, 1.01; 95% CI, 1.004–1.025; p = 0.015) were associated with a higher risk of fluid overload that was greater than 5%. Conclusions: Fluid overload in the early postoperative period was associated with higher mortality and morbidity. Risk factors for fluid overload include underlying kidney dysfunction, hemodynamic instability, and higher blood loss on the day of the surgery.

Down syndrome and postoperative complications after paediatric cardiac surgery: a propensity-matched analysis

OBJECTIVES The incidence of congenital heart disease is ~50%, mostly related to endocardial cushion defects. The aim of our study was to investigate the postoperative complications that occur after paediatric cardiac surgery. METHODS Our perioperative data were analysed in paediatric patients with Down syndrome undergoing cardiac surgery. We retrospectively analysed the data from 2063 consecutive paediatric patients between January 2003 and December 2008. After excluding the patients who died or had missing data, the analysed database (before propensity matching) contained 129 Down patients and 1667 non-Down patients. After propensity matching, the study population comprised 222 patients and 111 patients had Down syndrome. RESULTS Before propensity matching, the occurrences of low output syndrome (21.2 vs 32.6%, P = 0.003), pulmonary complication (14 vs 28.7%, P < 0.001) and severe infection (11.9 vs 22.5%, P = 0.001) were higher in the Down group. Down patients were more likely to have prolonged mechanical ventilation [median (interquartile range) 22 (9-72) h vs 49 (24-117) h, P = 0.007]. The total intensive care unit length of stay [6.9 (4.2-12.4) days vs 8.3 (5.3-13.2) days, P = 0.04] and the total hospital length of stay [17.3 (13.3-23.2) days vs 18.3 (15.1-23.6) days, P = 0.05] of the Down patients were also longer. Mortality was similar in the two groups before (3.58 vs 3.88%, P = 0.86) and after (5.4 vs 4.5%, P = 1.00) propensity matching. After propensity matching, there was no difference in the occurrence of adverse events. CONCLUSIONS After propensity matching Down syndrome was not associated with increased mortality or complication rate following congenital cardiac surgery.

Postoperative differences between colonization and infection after pediatric cardiac surgery-a propensity matched analysis.

BackgroundThe objective of this study was to identify the postoperative risk factors associated with the conversion of colonization to postoperative infection in pediatric patients undergoing cardiac surgery.MethodsFollowing approval from the Institutional Review Board, patient demographics, co-morbidities, surgery details, transfusion requirements, inotropic infusions, laboratory parameters and positive microbial results were recorded during the hospital stay, and the patients were divided into two groups: patients with clinical signs of infection and patients with only positive cultures but without infection during the postoperative period. Using propensity scores, 141 patients with infection were matched to 141 patients with positive microbial cultures but without signs of infection. Our database consisted of 1665 consecutive pediatric patients who underwent cardiac surgery between January 2004 and December 2008 at a single center. The association between the patient group with infection and the group with colonization was analyzed after propensity score matching of the perioperative variables.Results179 patients (9.3%) had infection, and 253 patients (15.2%) had colonization. The occurrence of Gram-positive species was significantly greater in the colonization group (p = 0.004). The C-reactive protein levels on the first and second postoperative days were significantly greater in the infection group (p = 0.02 and p = 0.05, respectively). The sum of all the positive cultures obtained during the postoperative period was greater in the infection group compared to the colonization group (p = 0.02). The length of the intensive care unit stay (p < 0.001) was significantly longer in the infection group compared to the control group.ConclusionsBased on our results, we uncovered independent relationships between the conversion of colonization to infection regarding positive S. aureus and bloodstream results, as well as significant differences between the two groups regarding postoperative C-reactive protein levels and white blood cell counts.

Chylothorax after pediatric cardiac surgery complicates short-term but not long-term outcomes—a propensity matched analysis

BACKGROUND The occurrence of postoperative chylothorax in children with congenital heart disease is a rare and serious complication in cardiac intensive care units (ICUs). The aim of our study was to identify the perioperative characteristics, treatment options, resource utilization and long term complications of patients having chylothorax after a pediatric cardiac surgery. METHODS Patients were retrospectively assessed for the presence of chylothorax between January 2002 and December 2012 in a tertiary national cardiac center. Occurrence, treatment options and long term outcomes were analyzed. Chylothorax patients less than 2 years of age were analyzed using propensity-matched statistical analysis in regard to postoperative complications after discharge. RESULTS During the 10-year period, 48 patients had chylothorax after pediatric cardiac surgery. The highest incidence was observed on the second postoperative day (7 patients, 14.6%). Seven patients (14.6% of the chylothorax population) died. During the follow up period, 5 patients had additional thromboembolic complications (2 had confirmed thrombophilia). Eleven patients had a genetic abnormality (3 had Downs syndrome, 3 had Di-Giorges syndrome, 1 had an IgA deficiency and 4 had other disorders). During the reoperations (49 cases), no chylothorax occurred. After propensity matching, the occurrence of pulmonary failure (P=0.001) was significantly higher in the chylothorax group, and they required prolonged mechanical ventilation (P=0.002) and longer hospitalization times (P=0.01). After discharge, mortality and neurologic and thromboembolic events did not differ in the matched groups. CONCLUSIONS Chylothorax is an uncommon complication after pediatric cardiac surgery and is associated with higher resource utilization. Chylothorax did not reoccur during reoperations and was not associated with higher mortality or long-term complications in a propensity matched analysis.

The impact of l-thyroxine treatment of donors and recipients on postoperative outcomes after heart transplantation

OBJECTIVE The effect of thyroid dysfunction on adverse outcomes has been studied in many different patient populations. The objective of this study was to investigate the effect of thyroid hormone supplementation of donors and recipients on postoperative outcomes after orthotopic heart transplantation. DESIGN Retrospective. SETTING Single center, university hospital. PARTICIPANTS Two-hundred and sixty-six consecutive patients undergoing heart transplantation. INTERVENTIONS No interventions. MEASUREMENTS AND MAIN RESULTS Demographic, hemodynamic, and clinical characteristics; donor and recipient United Network for Organ Sharing scores; and information on thyroid hormone support of donors and recipients were recorded. During the median follow-up of 4.59 years (interquartile range 4.26-4.92 y), 70 patients (26.3%) died. After adjustments were made for the United Network for Organ Sharing score, recipients who were treated preoperatively with l-thyroxine had a lower risk for all-cause mortality (adjusted hazard ratio [HR] 0.24, 95% confidence interval [CI] 0.06-0.98; p = 0.047) compared with recipients who were not treated with l-thyroxine. In addition, l-thyroxine treatment of donors was associated with a better recipient survival (HR 0.31, 95% CI 0.11-0.87; p = 0.025). CONCLUSIONS Pretransplantation thyroid hormone supplementation of donors and recipients was associated with improved long-term survival after heart transplantation.

Higher Transaminase Levels in the Postoperative Period After Orthotopic Heart Transplantation Are Associated With Worse Survival

OBJECTIVE Preoperative liver function in heart failure patients is associated with extensive functional, structural, and hemodynamic abnormalities. The authors hypothesized that perioperative liver dysfunction is associated with worse 2-year survival after orthotopic heart transplantation. DESIGN Retrospective study. SETTING Single-center, university hospital. PARTICIPANTS The study comprised 209 consecutive patients undergoing heart transplantation. INTERVENTIONS No interventions. MEASUREMENTS AND MAIN RESULTS Hepatobiliary markers, hemodynamic parameters, echocardiographic parameters, the need for mechanical cardiac support, demographic parameters, and United Network for Organ Sharing and Model for End-Stage Liver Disease (MELD) scores were investigated. Fifty-five patients (26.3%) died, and the mean survival time was 3.61 years after transplantation. In multivariate Cox regression analysis, in addition to the preoperative modified MELD score, the 4th quartiles of the maximum aspartate transaminase (AST) and alanine transaminase levels on the 4th through 7th postoperative days were independently associated with mortality (odds ratio [OR] 2.46, 95% confidence interval [CI] 1.09-5.55; p = 0.031 and OR 2.41, 95% CI 1.13-5.18; p = 0.024, respectively). By expressing the transaminase values as the multiplier of the sex-specific top normal value, the maximum AST and alanine transaminase levels (OR 1.02, 95% CI 1.01-1.02; p < 0.001 and OR 1.02, 95% CI 1.01-1.03; p = 0.001, respectively) were linked to worse survival. Among the postdischarge parameters, the modified MELD score (OR 1.17, 95% CI 1.09-1.27; p < 0.001) and the AST level were associated with postdischarge mortality (OR 1.002, 95% CI 1.001-1.003; p < 0.001 as a continuous variable; OR 1.07, 95% CI 1.05-1.10; p < 0.001, expressed as the multiplier of the sex-specific normal value, respectively). CONCLUSIONS The severity of postoperative liver dysfunction negatively influences survival after heart transplantation, and liver function should be closely assessed in these patients.

Aprotinin: Pharmacological Benefits and Safety

In cardiac surgery, perioperative blood transfusion carries considerable risk of complications and increases resource utilization. Antifibrinolytics, particularly aprotinin, have been used effectively to reduce bleeding and transfusion needs. In 2008, the manufacturer withdrew aprotinin from the market due to the discontinued “Blood conservation using Antifibrinolytics in a Randomized Trial” (BART) study, which showed an increased mortality associated with the usage of aprotinin [1]. The consensus conference held on June 8, 2011 in Milan identified aprotinin as a drug, which increases 30-day mortality after cardiac surgery [2, 3]. Recently, the database of the BART study was reanalyzed, and the European Medicines Agency and Health for Canada recommended lifting the suspension of aprotinin-containing medications [4, 5]. The purpose of this chapter is to describe the pharmacokinetic and pharmacodynamic properties of aprotinin and to discuss the literature evidences related to mortality.

Aprotinin: Pharmacological Benefits and Safety Concerns

In cardiac surgery, perioperative blood transfusion carries considerable risk of complications and increases resource utilization. Antifibrinolytics, particularly aprotinin, have been used effectively to reduce bleeding and transfusion needs. In 2008, the manufacturer withdrew aprotinin from the market due to the discontinued “Blood conservation using antifibrinolytics in a Randomized Trial” (BART) study, which showed an increased mortality associated with the use of aprotinin.