Safety and Quality-Improvement Initiative
abstract
OBJECTIVES:Venous thromboembolism (VTE) prophylaxis for patients at risk is often overlooked in pediatric health care institutions, which provides an opportunity to improve patient care. The objectives of this study were to review our current hospital practice, identify a popula-tion at high risk, and formulate institupopula-tional guidelines for throm-boprophylaxis.
METHODS:This was a prospective patient-safety and quality-improvement project performed at a large pediatric tertiary care hos-pital. We developed criteria for assessing risk and selecting prophylac-tic intervention through analysis of the age distribution and underlying medical conditions of patients with VTE at our center, literature review of adult recommendations for thromboprophylaxis, and consensus opinion of multiple specialists at our institution. A patient-care policy was developed to assess VTE risk and prescribe the appropriate thromboprophylaxis regimen. The primary outcome measure was compliance with thromboprophylaxis guidelines in patients at risk for VTE.
RESULTS:Over the 4-year study period, the observed rate of VTE pro-phylaxis in patients at risk increased from a baseline of 22% to an average rate of 82%, and there were intermittent improvements up to 100%.
CONCLUSIONS:Although some of the details may vary from center to center, many of the discussed principles and practices involved in instituting a VTE-prevention program are applicable to other pediatric institutions. Despite the fact that the risk of VTE in hospitalized children is much lower than that in adults, there are patients in pediatric hos-pitals who deserve systematic screening and thoughtful application of preventative measures.Pediatrics2011;127:e1326–e1332
AUTHORS:Leslie Raffini, MD,aTara Trimarchi, CRNP,b
Johanna Beliveau, RN, BSN,band Daniela Davis, MDc
aDivision of Hematology, Department of Pediatrics, andcDivision of Critical Care, Department of Anesthesia, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; andbCenter for Patient Quality and Safety, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
KEY WORDS
adolescent, anticoagulation, prophylaxis, thrombosis
ABBREVIATION
VTE—venous thromboembolism
All of the authors made substantive intellectual contributions to this study. Dr Raffini, Ms Trimarchi, and Dr Davis were involved in study concept and design, data analysis, and writing the manuscript, and Ms Beliveau was involved in data acquisition and analysis and preparation of the figures. All of the authors approved the final version of the manuscript.
www.pediatrics.org/cgi/doi/10.1542/peds.2010-3282 doi:10.1542/peds.2010-3282
Accepted for publication Nov 1, 2010
Address correspondence to Leslie Raffini, MD, Division of Hematology, Children’s Hospital of Philadelphia, 11022 CTRB, 3501 Civic Center Blvd, Philadelphia, PA 19104. E-mail: raffini@ chop.edu
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2011 by the American Academy of Pediatrics
Hospital-acquired venous thromboem-bolism (VTE) is a life-threatening con-dition that includes deep-vein throm-bosis and pulmonary embolism and is the most common preventable cause of hospital death in adults.1–3VTE can
also prolong length of stay, require in-vasive treatment, and result in chronic disability and the need for long-term anticoagulation treatment. Throm-boprophylaxis is highly effective at preventing VTE, and the Agency for Healthcare Research and Quality has identified thromboprophylaxis as the “number one patient safety practice.”4
Although the overall risk of VTE in hos-pitalized children is much lower than that in adults, there has been a signif-icant increase in VTE in pediatric ter-tiary care centers over the past de-cade.5 A proportion of these events
occur in hospitalized adolescents who share many of the risk factors that are associated with hospital-acquired VTE in adults.6Furthermore, pediatric
ter-tiary care hospitals frequently provide care to young adults with chronic med-ical conditions (eg, cystic fibrosis, con-genital heart disease, spina bifida) but often do not have established throm-boprophylaxis protocols for these adult patients. Query of the 2008 Pedi-atric Health Information System ad-ministrative database revealed that
⬎20% of patients admitted to tertiary care children’s hospitals are 14 years of age or older, and 6% are 18 years of age or older (unpublished data). Thus, although the incidence of hospital-acquired VTE is lower, there is a signif-icant population of patients who de-serve systematic screening and thoughtful application of preventative measures.
Randomized clinical trials for demon-strating the efficacy of prophylactic anticoagulation treatment in adults have required thousands of patients, used invasive imaging studies (venog-raphy), and are not feasible for
chil-dren. Nonetheless, the fact that hospital-acquired VTEs were occurring at our institution compelled us to launch this initiative. Our objectives were to review our current hospital practice, develop a risk assessment, and formulate institutional guidelines for thromboprophylaxis. The goal of this patient-safety and quality-improvement project was to improve the use of VTE prophylaxis in patients “at risk” to 90%. Clinical outcomes (de-velopment of VTE) were not systemati-cally collected as part of this study, al-though patients on anticoagulant medications were enrolled in a safety study.
PATIENTS AND METHODS
This project was a quality-improvement ac-tivity and exempt from review from the institutional review board at the Chil-dren’s Hospital of Philadelphia.
Guideline Development
Criteria for assessing risk and select-ing prophylactic interventions were developed through analysis of the age distribution and underlying medical conditions of patients with VTE by us-ing data from an ongous-ing prospective thrombosis cohort study that was de-scribed previously,7 literature review
of adult recommendations for throm-boprophylaxis,1,8and consensus
opin-ion of physicians at our institutopin-ion in the pediatric specialties (hematology, intensive care, adolescent medicine, orthopedics, general surgery, and re-habilitation). Although the presence of a central venous catheter is the most prevalent risk factor for VTE in pediat-ric patients, prevention of catheter-related thrombosis was not the pri-mary goal of these guidelines, because effective thromboprophylaxis in this setting has not been established.9 A
patient-care policy for prevention of VTE was written and approved by key stakeholders including the Executive Committee of the Medial Staff and
pre-sented to the Patient Safety Committee before implementation.
Implementation of Guidelines
Several interventions were instituted to encourage timely initiation of thromboprophylaxis. The new patient-care policy was publicized and pre-sented in numerous multidisciplinary educational forums to inform clini-cians. VTE risk assessment was incor-porated into the nursing admission-intake forms, and a VTE-prophylaxis order set was implemented into the computerized order-entry system. In the ICU, the nurses assess VTE risk and preventative practice daily during rounds with the care team. Various pneumatic compression devices were trialed with attention to appropriate sizing for pediatric patients. The num-ber of these devices was increased, and they were stored at point of use in high-risk areas (the ICUs and in each operating room). A protocol for periop-erative nurses to initiate pneumatic compression before the start of surgi-cal procedures for all patients 14 years of age or older who were under-going a procedure ofⱖ45 minutes’ du-ration was developed and later ex-panded to all inpatient settings.
Measures of Compliance
To determine the use of VTE prophy-laxis before instituting guidelines, baseline data were collected intermit-tently during the 6-month period of guideline development. The percent-age of patients who received appropri-ate thromboprophylaxis according to the guidelines was measured monthly via random audits on inpatient units, and since May 2009 the PICU has per-formed weekly audits.
regression was used to assess the re-lationship of compliance over time.
Measures of Safety
As part of a separate institutional re-view board–approved study, we have been enrolling patients (after obtain-ing informed consent) who receive anti-coagulation prophylaxis onto a prospec-tive cohort study to evaluate the safety and tolerability of prophylactic anticoag-ulation treatment. This study includes data on patient demographics, risk fac-tors for VTE, dose and duration of antico-agulation medication, and thrombotic and bleeding complications.
RESULTS
Risk Stratification
Results of a review of the age distribu-tion of patients with VTE at our institu-tion were consistent with those of pre-viously published studies; there was a peak in neonates and adolescents (Fig 1). The increasing risk during adoles-cence correlates with full maturation of the hemostatic system.10 Further
evaluation revealed that among pa-tients aged 14 years or older with VTE in our thrombosis cohort from Janu-ary 2003 to May 2006, 47% (48 of 102) of the cases of VTE were “hospital-acquired,” although 35 of them were catheter-related thrombotic events. Fif-teen percent (15 of 102) of VTEs in pa-tients aged 14 years or older were hospital-acquired non– catheter-related VTEs (Fig 1). There was considerable discussion regarding whether to choose an absolute age cutoff or a spe-cific pubertal development stage at which to consider prophylaxis. Ulti-mately, the age of 14 years was chosen as a somewhat conservative cutoff age for VTE risk assessment, and we made the following provisions: (1) patients younger than 14 years could receive
prophylaxis at the discretion of the treating physician; and (2) the proto-col could later be modified if it was felt that this cutoff resulted in undertreatment.
The algorithm for risk stratification and thromboprophylaxis is shown in Fig 2. Hospitalized patients aged 14 years or older are evaluated and strat-ified into categories on the basis of risk factors. The VTE risk factors were established by using data from our co-hort as well as other published risk factors for pediatric and adult VTE. Am-bulatory patients without additional VTE risk factors are considered to be at low risk; patients with at least 1 risk factor for VTE are considered to be at risk; and those with altered mobility (immobile or impaired physical mobil-ity) who have at least 1 additional risk factor for VTE are considered to be at high risk for developing VTE. We admit that the categorization of altered mo-bility is somewhat objective, although we chose to define it on the basis of a nursing standard from our institution (Fig 2).
Options for Thromboprophylaxis
Interventions for VTE prevention in our policy included early and frequent am-bulation (within 12 hours of hospital-ization or surgery), mechanical
pro-phylaxis using graduated compression antiembolic stockings or sequential pneumatic compression, and/or anti-coagulant prophylaxis with
enoxa-parin or unfractionated heenoxa-parin. For immobile patients, sequential pneu-matic compression is preferred over antiembolic stockings because of the active (rather than passive) compres-sion. Because enoxaparin is the most frequently prescribed low molecular weight heparin in pediatrics, it was chosen as the preferred anticoagu-lant, although unfractionated heparin was also included, at a dose of 5000 U subcutaneous twice daily, because it was the preferred anticoagulant of the neurosurgeons.
Prophylactic dosing of enoxaparin in patients⬎60 kg is either 30 mg
subcu-taneous twice daily, an accepted dos-ing regimen for adult orthopedic sur-gery patients,8or 40 mg once daily, an
accepted dosing regimen for adult medical patients. Prophylactic dosing of enoxaparin for patients⬍60 kg is 0.5 mg/kg subcutaneous twice daily, based on current dosing recommen-dations for pediatric patients.9
Hepa-rin anti-Xa levels are not routinely monitored in patients who receive thromboprophylaxis at our center un-less the patient has renal insufficiency.
FIGURE 1
In the postoperative setting, we recom-mend initiating anticoagulant prophy-laxis 12 to 24 hours after surgery, one of the standard acceptable regimens for adult orthopedic surgery.8
Contraindica-tions to anticoagulant prophylaxis in-cluded recent intracranial hemorrhage (⬍7 days), acute stroke, active bleeding, uncorrected coagulopathy, incomplete spinal cord injury with suspected or proven paraspinal hematoma, allergy to pork products, and heparin-induced thrombocytopenia.8
Guidelines for Thromboprophylaxis
Recommendations for thrombopro-phylaxis based on risk assessment are outlined in Fig 2. The decision to use anticoagulant prophylaxis in patients at high risk is made by the patient’s attending physician. A hematology con-sultation can be requested but is not
necessary to initiate anticoagulant thromboprophylaxis.
Compliance With Guidelines
As a result of the project, the observed rate of VTE prophylaxis in patients who met clinical criteria for being at risk or at high risk increased from a baseline average rate of 22% (range: 0%– 40%), which was determined by mul-tiple small random audits during the 4-month period of guideline develop-ment, to an average rate of 82% (1216 of 1484 screened patients), and there were intermittent im-provements up to 100% (Fig 3). There was a highly significant increase in thromboprophylaxis use over time (P ⬍ .001). The number of patients screened varied throughout the study period, in part on the basis of available resources at the time.
Since May 2009, there have been 217 patients at risk and 120 patients at high risk screened in our PICU. Of the 120 patients at high risk, 58 (48%) re-ceived pharmacologic anticoagulation (often along with mechanical prophy-laxis), whereas 71 of the remaining 72 patients received isolated mechanical prophylaxis. Similarly, 344 patients at risk and 88 patients at high risk have been screened throughout the remain-ing hospital units. Of the 88 patients at high risk, 22 (25%) received pharma-cologic anticoagulation.
The improvement in compliance was incremental, and multiple gains in im-provement were temporally related to specific interventions including publi-cation of the patient-care policy (May 2006), nursing initiation of sequential compression devices (October 2006), the addition of VTE risk assessment to
FIGURE 2
Algorithm for inpatient VTE risk assessment and prophylaxis. DVT indicates deep-vein thrombosis; PE, pulmonary embolism; SQ, subcutaneous; BID, twice daily; uFH, unfractionated heparin.
the nursing admission database, and nursing education (July 2007). In addi-tion, success of the project was evi-dent by the phenomenon of front-line nursing staff who expressed interest in maintaining responsibility for as-sessing patients for risk and for initi-ating mechanical prophylaxis mea-sures. This interest spiked when the nursing staff recognized that there was an insufficient number of pneu-matic compression devices to meet the needs of all patients at risk. Trials of new devices were held, which pro-vided service education and in-creased awareness of the issue.
Ongoing measurements of compliance have served to identify barriers to the use of thromboprophylaxis that can be addressed to promote improvement. For example, continuous prompts at the point of care such as the inclusion of VTE risk assessment and prophy-laxis plan on admission and perioper-ative documentation tools have helped to hard-code practices into daily rou-tine. In addition, requests by front-line
nurse practitioners and physicians to add customized VTE prophylaxis to their existing admission order sets in the computerized patient order-entry system have indicated that awareness
of the issue has also increased among prescribing clinicians.
In addition to evaluating compliance
via random audits, all cases of patients older than 14 years who develop non– catheter-related hospital-acquired VTE are reviewed by a multidisciplinary team to determine if adequate VTE pro-phylaxis was administered. These
cases provide ongoing information on how to improve VTE prophylaxis. In 2010, after a young adult patient devel-oped a hospital-acquired VTE, the algo-rithm was modified to reflect the pref-erence for pharmacologic prophylaxis
in patients at high risk who are older than 21 years (shaded area in Fig 2). Again, the age of 21 was somewhat conservative and was chosen with the understanding that it could be lowered (to 18 years) if not sufficient.
Safety
We have enrolled more than 90 pa-tients into our prospective safety eval-uation, and there have been no major bleeding complications related to the use of anticoagulation prophylaxis. The results of this study will be re-ported in greater detail in a subse-quent article.
DISCUSSION
VTE prophylaxis for patients at high risk is often overlooked in pediatric health care institutions, which pro-vides an opportunity to improve pa-tient safety. One of the greatest chal-lenges in the field of pediatric thrombosis is the lack of randomized clinical trials to guide treatment. None-theless, standard practices for treat-ing pediatric patients with VTE, largely extrapolated from adult guidelines, do exist, and there are results from many large cohort studies to support these practices.9 In a similar fashion, we
prevention in pediatric hospitals. At a minimum, pediatric hospitals should follow adult thromboprophylaxis guidelines for patients older than 18 years.1
To our knowledge, there are only 3 publications that have addressed thromboprophylaxis in children.9,11The
American Academy of Chest Physicians guidelines for antithrombotic therapy in children and neonates provide spe-cific recommendations for throm-boprophylaxis in limited circum-stances including arterial catheters, heart valves, dilated cardiomyopathy, and specific congenital heart defects.11
These guidelines recommend against the use of routine anticoagulant pro-phylaxis for patients with central venous catheters. A second publica-tion provided guidelines for throm-boprophylaxis for children undergoing surgery; the authors used an unvali-dated scoring system for VTE risk that included the following variables: age; congenital heart disease; preexist-ing medical problems, includpreexist-ing pre-vious thrombosis; current medical problems; medications, including oral contraceptives; and central ve-nous catheters.11 Most recently, a
predictive model to assess VTE risk in pediatric patients with leukemia was published, suggesting a reduc-tion of VTE in high risk patients treated with enoxaparin.12
The guidelines for VTE prevention pre-sented here may change over time as new data become available. Nearly 20% of patients admitted to tertiary care hospitals that participate in the Pediatric Health Information System database are older than 14 years.
Al-though it would be valuable to identify and study all inpatients at risk and their outcomes in a prospective study, we currently do not have the re-sources for such an endeavor.
Our current guidelines permit the at-tending physician to ultimately deter-mine if a patient at high risk should receive sequential compression or an-ticoagulation treatment. We allowed this flexibility because we felt that the lack of evidence in pediatrics made it difficult to stipulate that all patients at high risk should receive anticoagula-tion treatment, the subcutaneous ad-ministration of which causes discom-fort and is not without risk. In the PICU, nearly half of all patients at high risk receive anticoagulant prophylaxis, compared with 25% in other inpatient units. A majority of remaining patients at high risk have received sequential pneumatic compression. Although it is well accepted that sequential com-pression is not as effective as antico-agulation for prophylaxis, there are data demonstrating that it does signif-icantly reduce the risk of VTE.13Over
time, the use of anticoagulant prophy-laxis at our hospital has increased as providers have become more experi-enced and comfortable with its use.
Our preliminary data suggest that the rate of major bleeding complications in adolescent patients on prophylaxis is low (0 of 90). We acknowledge that demonstrating the safety of our algo-rithm is a critical component, and we plan to continue to monitor it.
Ongoing improvement efforts include education of newly established inpatient-unit quality and safety teams to perform audits on their own units,
which will help identify barriers to the use of prophylaxis and allow for “just-in-time” training to educate clinical staff at the time of audits. In addition, the project team reviews and tracks cases of non– catheter-related hospital-acquired VTE to determine if appropri-ate prophylaxis was administered and whether guidelines need to be modi-fied. This process may allow for a com-parison of hospital-acquired VTE be-fore and after implementation of our guidelines, although it will be compli-cated by the difficulty in obtaining an accurate denominator (patients at risk) for the study periods.
CONCLUSIONS
The risk criteria and practices recom-mended in this policy are applicable to other pediatric institutions. Although some of the specific details may vary from center to center, many of the practices and principals involved in in-stituting a VTE-prevention program will be the same. In addition to increas-ing the use of VTE prophylaxis at our pediatric institution, this project has the potential to heighten general awareness of VTE risk in the pediat-ric health care community, provide the foundation for pediatric VTE-prevention programs throughout the country, and facilitate much needed multicenter outcomes research on the incidence, prevention, and treatment of VTE in children.
ACKNOWLEDGMENTS
We acknowledge Kathy Shaw, MD, An-nette Bollig, Donna Schilling, Heidi Martin, and Elizabeth Moxey for their helpful feedback and ongoing support of this project.
REFERENCES
1. Geerts WH, Bergqvist D, Pineo GF, et al; Amer-ican College of Chest Physicians. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).Chest. 2008; 133(6 suppl):381S– 453S
2. Shojania KG, Duncan BW, McDonald KM, Wa-chter RM, Markowitz AJ. Making health care safer: a critical analysis of patient safety practices.Evid Rep Technol Assess (Summ). 2001;(43):i–x, 1– 668
3. Tapson VF, Hyers TM, Waldo AL, et al.
Anti-thrombotic therapy practices in US hospi-tals in an era of practice guidelines.Arch Intern Med. 2005;165(13):1458 –1464 4. Society of Hospital Medicine, Maynard G,
and Stein J; Agency for Healthcare Re-search and Quality. Preventing
Available at: www.ahrq.gov/qual/vtguide. Accessed March 14, 2011
5. Raffini L, Huang YS, Witmer C, Feudtner C. Dramatic increase in venous thromboem-bolism in children’s hospitals in the United States from 2001 to 2007.Pediatrics. 2009; 124(4):1001–1008
6. Andrew M, David M, Adams M, et al. Ve-nous thromboembolic complications (VTE) in children: first analyses of the Ca-nadian Registry of VTE.Blood. 1994;83(5): 1251–1257
7. Raffini LJ, Raybagkar D, Blumenstein MS, Rubenstein RC, Manno CS. Cystic fibrosis as
8. Geerts WH, Pineo GF, Heit JA, et al. Preven-tion of venous thromboembolism: the Sev-enth ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004; 126(3 suppl):338S– 400S
9. Monagle P, Chalmers E, Chan A, et al; Amer-ican College of Chest Physicians. Antithrom-botic therapy in neonates and children: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 suppl): 887S–968S
10. Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L. Maturation of the
hemo-thromboprophylaxis in children: develop-ment of a guideline for managedevelop-ment. Paedi-atr Anaesth. 2008;18(6):478 – 487
12. Mitchell L, Lambers M, Flege S et al. Valida-tion of a predictive model for identifying an increased risk for thromboembolism in c h i l d r e n w i t h a c u t e l y m p h o b l a s t i c leukemia: results of a multicenter cohort study.Blood. 2010;115(24):4999 –5004 13. Urbankova J, Quiroz R, Kucher N, Goldhaber
SZ. Intermittent pneumatic compression and deep vein thrombosis prevention: a meta-analysis in postoperative patients.
DOI: 10.1542/peds.2010-3282 originally published online April 4, 2011;
2011;127;e1326
Pediatrics
Leslie Raffini, Tara Trimarchi, Johanna Beliveau and Daniela Davis
Quality-Improvement Initiative
Thromboprophylaxis in a Pediatric Hospital: A Patient-Safety and
Services
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