National pediatric anesthesia safety quality improvement program in the United States.

BACKGROUND: As pediatric anesthesia has become safer over the years, it is difficult to quantify these safety advances at any 1 institution. Safety analytics (SA) and quality improvement (QI) are used to study and achieve high levels of safety in nonhealth care industries. We describe the development of a multiinstitutional program in the United States, known as Wake-Up Safe (WUS), to determine the rate of serious adverse events (SAE) in pediatric anesthesia and to apply SA and QI in the pediatric anesthesia departments to decrease the SAE rate. METHODS: QI was used to design and implement WUS in 2008. The key drivers in the design were an organizational structure; an information system for the SAE; SA to characterize the SAE; QI to imbed high-reliability care; communications to disseminate the learnings; and engaged leadership in each department. Interventions for the key drivers, included Participation Agreements, Patient Safety Organization designation, IRB approval, Data Management Co., membership fee, SAE standard templates, SA and QI workshops, and department leadership meetings. RESULTS: WUS has 19 institutions, 39 member anesthesiologists, 734 SAE, and 736,365 anesthetics as of March, 2013. The initial members joined at year 1, and initial SAE were recorded by year 2. The SAE rate is 1.4 per 1000 anesthetics. Of SAE, respiratory was most common, followed by cardiac arrest, care escalation, and cardiovascular, collectively 76% of SAE. In care escalation, medication errors and equipment dysfunction were 89%. Of member anesthesiologists, 70% were trained in SA and QI by March 2013; virtually, none had SA and QI expertise before joining WUS. CONCLUSION: WUS documented the incidence and types of SAE nationally in pediatric anesthesiology. Education and application of QI and SA in anesthesia departments are key strategies to improve perioperative safety by WUS.

Use of recombinant factor VIIa for uncontrolled bleeding in neonates after cardiopulmonary bypass.

BACKGROUND: Increasingly, recombinant activated factor VII (rFVIIa) is used adjunctively in nonhemophiliacs to control hemorrhage unresponsive to conventional therapy in a variety of settings including postcardiopulmonary bypass (CPB). Studies examining rFVIIa administration to neonates after CPB are limited. The goal of this study was to evaluate retrospectively the clinical outcomes of neonates treated at our institution with rFVIIa for uncontrolled post-CPB bleeding. METHODS: We retrospectively identified eight neonates undergoing complex congenital cardiac surgery who received rFVIIa, either intraoperatively or postoperatively, for uncontrolled post-CPB bleeding. Transfusion trends and prothrombin times (PT) were assessed both pre- and post-rFVIIa administration. Chest tube drainage volumes were recorded pre- and post-rFVIIa administration in those neonates receiving rFVIIa postoperatively in the intensive care unit. We documented such adverse events as thrombosis, dialysis (hemodialysis and peritoneal dialysis), extracorporeal membrane oxygenation (ECMO) and in-hospital mortality. RESULTS: The mean amount of transfused packed red blood cells, platelets and fresh frozen plasma decreased significantly after the administration of rFVIIa. Transfusion of cryoprecipitate trended towards a decrease but did not reach statistical significance. PT values also decreased significantly after the administration of rFVIIa. A high mortality was found in neonates exposed to both rFVIIa and ECMO; however, this was not significantly different from the mortality of neonates exposed to ECMO alone. CONCLUSIONS: Administration of rFVIIa to neonates for the treatment of uncontrolled post-CPB bleeding significantly reduced transfusion requirements and normalized PT values. Future randomized, controlled trials are needed to evaluate the potential hemostatic benefit and adverse effects of rFVIIa administration to neonates following CPB.

The impact of aprotinin on postoperative renal dysfunction in neonates undergoing cardiopulmonary bypass: a retrospective analysis.

BACKGROUND: Recent concern about the safety of aprotinin administration to adults has led to its suspension from worldwide markets. However, few studies have examined its safety in pediatric patients. Studies in children evaluating aprotinin's safety have been hindered by the heterogeneity of pediatric patients and the inconsistency of clinical protocols. In this investigation, we retrospectively reviewed 200 neonatal cardiac surgical cases performed at our institution to examine the safety of aprotinin, focusing on postoperative renal dysfunction, using a consistent aprotinin dosing protocol. METHODS: Two-hundred consecutive neonates scheduled for palliative or corrective congenital cardiac surgery requiring cardiopulmonary bypass (CPB) from January 1, 2005 through February 28, 2007 were included in this retrospective investigation. Preoperative, intraoperative and postoperative data were collected and analyzed. Markers of safety included 72-h postoperative renal dysfunction, need for dialysis (peritoneal or hemodialysis), thrombosis and in-hospital mortality. RESULTS: Neonates were divided into those who received aprotinin (aprotinin group; n = 156) and those who did not (no aprotinin group; n = 44). Twenty-four and 72-h postoperative serum creatinine levels were significantly greater than baseline levels in both groups. The degree of change in creatinine levels was highly significant and similar between the two groups. A larger percentage of neonates in the aprotinin group developed renal dysfunction, although this difference was not statistically significant. Stepwise logistic regression, assessing the impact on renal dysfunction of all variables that indicated significance between neonates who did or did not receive aprotinin and between neonates who did or did not develop renal dysfunction, identified CPB time and age as significant predictors of postoperative renal dysfunction. All neonates who developed postoperative renal dysfunction had a CPB time of more than 100 min regardless of the use of aprotinin. Additionally, using this subset, similar percentages of renal dysfunction occurred in both groups. A second multivariable regression analysis to simultaneously account for the predictors of CPB time, age and aprotinin administration found CPB time to be the only significant predictor of renal dysfunction. Incidences of postoperative dialysis, postoperative thrombosis and in-hospital mortality were not statistically significantly different between the aprotinin and the no aprotinin groups. CONCLUSION: The occurrence of postoperative renal dysfunction in neonates was more significantly predicted by the duration of CPB than by the intraoperative administration of aprotinin. CPB times of more than 100 min appeared to be a critical marker for the development of postoperative renal dysfunction. Randomized prospective trials are needed to confirm the validity of our retrospective findings.

A comparison of heparin management strategies in infants undergoing cardiopulmonary bypass.

BACKGROUND: Recent investigations in adult patients have suggested that a heparin concentration-based anticoagulation protocol for heparin administration during cardiopulmonary bypass (CPB) significantly reduced hemostatic activation when compared with standard weight-based heparin doses. Reductions in hemostatic activation during CPB could be particularly beneficial in pediatric patients in whom CPB-related coagulation issues are complex and influenced by many variables. However, information regarding heparin levels during CPB and their correlation to hemostatic activation is lacking in children. In this investigation, we compared a patient-specific heparin concentration-based heparin management protocol with a standard weight-based protocol in infants <6-mo-of-age. The efficacy of these two protocols was assessed by comparisons of heparin concentration, levels of biochemical markers of hemostatic activation, and clinical outcome. METHODS: Twenty-five infants <6-mo-old scheduled for primary, elective repair of a congenital heart defect were enrolled in this study. Patients were randomized to receive either 400 U/kg of heparin (control group) or a patient-specific heparin dose calculated by the Hepcon Hemostasis Management System Plus (Hepcon HMS; Medtronic, Minneapolis, MN; intervention group). Heparin concentrations were compared between the two groups at predetermined intervals. Blood samples for biochemical markers of hemostatic activation were collected before and after CPB, and measurements of clinical outcome were recorded. RESULTS: Infants in the intervention group received a larger total heparin dose than infants in the control group. Heparin concentrations after the initial heparin dose and 30 min into CPB were similar between groups; however, at the start of rewarming and at the termination of CPB, infants in the intervention group had significantly higher heparin concentrations than infants in the control group. Infants in the intervention group also generated less F1.2 and consumed less factor VIII than infants in the control group. Clinically, however, infants in the intervention group received one more donor exposure from the administration of blood products post-CPB. CONCLUSION: A heparin concentration-based heparin management protocol in infants <6-mo-old resulted in higher, more constant heparin concentrations during CPB than a standard weight-based protocol. Furthermore, higher heparin concentrations were associated with greater suppression of hemostatic activation, as measured by less generation of thrombin and less consumption of factor VIII. Our findings demonstrate that use of a patient-specific heparin concentration-based protocol for heparin administration during CPB in infants may attenuate hemostatic activation. However, further research is needed to determine if this protocol has clinically beneficial hemostatic effects.

Clinical measures of heparin's effect and thrombin inhibitor levels in pediatric patients with congenital heart disease.

In this investigation, we examined the relationship among three thrombin inhibitors, antithrombin III (ATIII), heparin cofactor II (HCII), and alpha-2-macroglobulin (alpha2M), and several clinical tests of heparin's effect in pediatric patients with congenital heart disease undergoing cardiopulmonary bypass. One hundred eighteen children were stratified into six age groups: <1 mo, 1-3 mo, 3-6 mo, 6-12 mo, 12-24 mo, and >10 yr. Baseline ATIII, HCII, and alpha2M values were measured. Baseline celite- and kaolin-activated clotting times (ACT) were also measured and repeated 3 min after a standard heparin dose of 400 U/kg. Differences in ACT values before and after heparin administration and a heparin dose-response relationship were calculated for each patient. Kaolin-activated ACT tests showed less variation after heparin administration than celite-activated tests. In contrast to what has been demonstrated in adults, ATIII showed no positive correlation with the clinical tests of heparin's effect nor did the other thrombin inhibitors. Additionally, patients <1 mo old had unexpectedly low levels of alpha2M accompanying their expected low levels of ATIII and HCII. Our findings raise concerns about the ability of heparin to adequately anticoagulate these neonates during cardiopulmonary bypass and, consequently, challenge the accuracy of ACT prolongation to truly reflect the extent of their anticoagulation.

An evaluation of the effects of a standard heparin dose on thrombin inhibition during cardiopulmonary bypass in neonates.

We compared the adequacy of heparinization in neonates and older children undergoing cardiopulmonary bypass (CPB) by measuring heparin activity, thrombin formation, and thrombin activity. Ten neonates and 10 older children were administered 400 U/kg of heparin before CPB. Heparin anti-Xa activity, prothrombin fragment 1.2 (F1.2), and fibrinopeptide A (FPA) were measured at baseline, after 30 min on CPB, immediately post-CPB, and 3 and 24 h post-CPB. Heparin anti-Xa activity was significantly decreased during and immediately post-CPB in the neonatal group. F1.2 and FPA levels in neonates were significantly higher at baseline, decreased with the commencement of CPB, and increased to levels higher than those in older children after CPB. Our data show that with standard heparin doses, neonates exhibit less heparin anti-Xa activity during CPB. Higher baseline levels of F1.2 and FPA present in neonates indicate preoperative activation of their coagulation systems as compared with older children. Although F1.2 and FPA levels initially decrease with the commencement of CPB, probably representing hemodilution, the subsequent increase in these markers indicates significantly more thrombin formation and activity during and after CPB. These results raise the concern that 400 U/kg of heparin may not adequately suppress thrombin formation and activity in neonates undergoing CPB.

The short term effects of cardiopulmonary bypass on neurologic function in children and young adults.

OBJECTIVE: Cognitive deficits are common in adults following surgery utilizing cardiopulmonary bypass (CPB). A previous retrospective study suggested that surgical closure of an ASD in children was associated with neurologic injury, while transcather therapy was not. In a prospective study, we sought to determine whether neurologic deficits occur following repair of non-complex congenital heart lesions in school-age children and young adults. METHODS: Inclusion criteria were: age between 5 and 20 years, cardiac surgery utilizing CPB without deep hypothermic circulatory arrest, and no prior cardiac surgery. Patients underwent psychometric testing 1-3 days prior to surgery and re-evaluation 7-18 days after surgery. In order to determine the test/re-test effect an age-matched cohort of children undergoing transcather closure of ASD under general anesthesia was also evaluated. The primary outcome measures were verbal and picture memory. Additional psychometric tests included: computerized performance test (CPT) and Digit Span (DS). Forty-one patients were enrolled, 29 undergoing surgery with CPB and 12 controls. Surgical procedures included ASD closure (n=13), VSD closure (n=10), resection of sub-aortic stenosis (n=3), mitral valvuloplasty (n=3). Mild hypothermia was used in all cases. The mean duration of CPB was 54+/-22 min. RESULTS: There was no significant difference in any of the psychometric test scores between subjects undergoing surgery with CPB or controls. CONCLUSIONS: There are no marked adverse neurologic effects of CPB in school-age children and young adults undergoing non-complex open-heart surgery. These data are important in counseling patients and families and should be considered in the debate as to the relative merits of transcather versus open-heart repair of various heart lesions.

Fibrinogen in children undergoing cardiac surgery: is it effective?

There is speculation based on laboratory tests and biochemical data regarding the functional integrity of the fibrinogen in young children. Recent investigations in adults have demonstrated that their fibrinogen level correlates with the thromboelastogram maximum amplitude (MA) after modification with a glycoprotein IIb/IIIa receptor blocker that uncouples platelet-fibrinogen interactions. We postulate that if the fibrinogen of young children is functionally intact then their fibrinogen levels should also correlate with modified thromboelastogram MA values as they do in adults. We compared modified and unmodified thromboelastogram variables of 250 children <2 yr old undergoing cardiac surgery with their fibrinogen levels and platelet counts. Five age groups were distinguished to determine if and when correlations become significant (<1 mo, 1-3 mo, 3-6 mo, 6-12 mo, and 12-24 mo). Fibrinogen levels correlated with modified thromboelastogram MAs only in the 12-24 mo group. In this 12-24 mo age group other correlations between fibrinogen levels and thromboelastogram variables influenced by fibrinogen also became significant, as did correlations noted in adults between platelet counts and thromboelastogram variables. We conclude that the fibrinogen of children <12 mo old with congenital heart disease is qualitatively dysfunctional.

Tissue factor-activated thromboelastograms in children undergoing cardiac surgery: baseline values and comparisons.

UNLABELLED: Activation of clotting with tissue factor (TF) allows rapid evaluation of thromboelastograms but alters the values of thromboelastogram variables. We have performed TF-activated thromboelastograms in 250 children <2 yr old undergoing cardiac surgery to establish baseline values. Five groups were distinguished to evaluate the effects of quantitative deficiencies in coagulation factor levels during infancy: <30 days, 1-3 mo, 3-6 mo, 6-12 mo, and 12-24 mo. Activation of clotting (R and K values) was similar among groups. Infants 1-3 mo of age demonstrated increased clot strength compared with the other groups, a finding similar to previous evaluation of native thromboelastograms. The alpha and maximum amplitude values were numerically almost identical in each age group, a unique finding in activated thromboelastograms. Fibrinolysis was similar among groups. We believe that knowledge of baseline TF-activated thromboelastogram variables in young children will be useful in interpreting these thromboelastograms in clinical scenarios, in using these thromboelastograms as part of coagulopathy treatment algorithms, and during the application of more specific thromboelastogram modifiers. Additionally, the similarity of alpha and maximum amplitude values in each age group will allow even faster interpretation of thromboelastogram data. IMPLICATIONS: Baseline values for tissue factor-activated thromboelastograms in young children undergoing cardiac surgery have been established and will permit accurate use and interpretation of this thromboelastogram modification in evaluating and managing coagulopathies.