BLOODSTREAM INFECTION/TRANSFUSION MEDICINE
Educational Objectives
| The goals of this program are to improve prevention of catheter-related bloodstream infections (CRBSI) and improve transfusion
medicine. After hearing and assimilating this program, the clinician will be better able to:
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 | 1. Explain the epidemiology and costs associated with CRBSI.
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| 2. Reduce the incidence of CRBSI using simple strategies and readily available technologies.
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| 3. Review the risks associated with blood transfusion.
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| 4. Discuss minimally acceptable hemoglobin levels.
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| 5. Examine data supporting a conservative strategy for blood transfusion.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning
committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts
of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health
care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Gropper
is a consultant for Cook, Inc. Dr. Brudney is a member of the Speaker’s Bureau for Hospira Pharmaceuticals. The planning
committee reported nothing to disclose.
Acknowledgements
Dr. Gropper spoke in Universal City, CA, at the California Society of Anesthesiologists’ Annual Meeting and Clinical
Anesthesia Update, held May 30 to June 1, 2008; Dr. Brudney was recorded in Kansas City, MO, at the 58th Annual
Postgraduate Symposium on Anesthesiology, held April 4-6, 2008, and sponsored by the University of Kansas
Medical Center, Departments of Anesthesiology and Continuing Education. The Audio-Digest Foundation thanks the
speakers and the sponsors for their cooperation in the production of this program.
| PREVENTING CATHETER-RELATED BLOODSTREAM INFECTION: THE ROLE OF THE
ANESTHESIOLOGIST— Michael A. Gropper, MD, PhD, Professor and Vice Chair, Department of Anesthesia and Perioperative
Care, Director, Critical Care Medicine, and Chair for Medical Quality, University of California, San Francisco,
School of Medicine
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| Nosocomial infections: anesthesiologists place ≈40% of central lines in United States; 2 million hospital-acquired infections
result in ≈90,000 deaths per year; ≈$5 billion in hospital costs; large percentage of nosocomial infections attributed
to catheter-related bloodstream infection (CRBSI)
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| Intensive care unit (ICU) infections: ventilator-associated pneumonia most common infection in medical and surgical
ICUs; CRBSI second or third most common infection
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| Epidemiology of CRBSI: ≈5 million central venous catheters inserted annually; 3% to 5% of catheters become infected;
associated mortality rates 5% to 35%
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| Costs of CRBSI: Shorr study found each incident costs ≈$60,000; speaker’s analysis estimated cost at ≈$80,000 per infection;
beginning October 1, 2008, federal government no longer will reimburse hospitals for costs associated with these
complications; currently, federal government and, to some extent, general public, attribute culpability to hospital and
staff (true in 99% of cases)
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| Institute for Healthcare Improvement (IHI): patient safety organization (www.ihi.org); public fear about hospital
safety increases media coverage; organization began 100,000 Lives Campaign; campaign goals—save 100,000 lives
across United States (over ≈18 mo) by preventing medical errors; enroll 2000 hospitals; change national infrastructure;
recommended changes—creation of rapid response teams (consisting of, eg, nurses, physicians, respiratory therapists)
who identify poorly performing patients who may require resuscitation (resuscitate before arrest); appropriate care for
patients with myocardial infarctions (MI; eg, giving aspirin; obtaining angioplasty in timely manner); prevention of adverse
drug events, central line infections, surgical site infections, and ventilator-associated pneumonia
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| Joint Commission on Accreditation of Hospital Organizations (JCAHO): all identified cases of unanticipated
death or major permanent loss of function associated with health care–associated infection should be managed as
sentinel events
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| Public reporting: many states mandate public reporting of nosocomial infections; reporting not standardized; government
must ensure hospitals report honestly; in California, hospitals must report every central line inserted in ICU (adult
or pediatric), including details on how line inserted, occupation of inserter (eg, attending physician, fellow, intern), reason
for insertion, compliance with sterile technique, and type of catheter; data collection and management pose significant
logistical challenges
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| Pay for performance: rewards quality with financial incentive large enough to encourage structural change; Centers
for Medicare and Medicaid Services (CMS) soon will withhold payments for care associated with treating certain hospital-associated
infections (eg, catheter-associated urinary tract infections, vascular catheter-associated infections) and for
other medical errors (eg, injuries resulting from falls; pressure ulcers; surgical objects left in patients; air emboli)
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| Potential sources of CRBSI: contamination by patient’s skin flora (most common source); early infections associated
with insertion technique; intraluminal infections resulting from contamination of device hubs by medical personnel; other
infections (eg, peritonitis) sometimes spread to line
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| Biofilm: protects organisms from antibiotics; may form around any device; allows bacteria to multiply; reduces exposure
to antibiotics, thereby stimulating development of resistance
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| Diagnosis of CRBSI: no gold standard; many possible sources of infection; more recent quantitative approaches helpful;
differential time depositivity—blood samples taken from catheter and arm (using sterile technique); laboratory
grows cultures; catheter contamination likely if catheter sample grows bacteria ≥2 hr faster than sample taken from arm
(catheter should be removed)
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| Start with prevention: education important (develop curriculum); prevention bundle includes hand hygiene, maximal
barrier precautions, chlorhexidine skin antisepsis, optimal catheter site selection (speaker tends to use internal jugular
vein under ultrasonography [US] guidance; data suggest safely placed subclavian line has lower infection rate than other
lines), US guidance, and daily review of line necessity with prompt removal of unnecessary lines
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| Eliminate central line infections: most ICUs benchmark rates of CRBSI; Johns Hopkins study targeted zero central
line infections; prospective trial compared 2 ICUs (general surgery and cardiac surgery); interdisciplinary team created;
interventions included education (web-based training module), central-line insertion cart, daily assessment of need for
catheter, bedside checklist completed by nursing staff (filled out during line insertion), and empowering nurses to stop
procedure if guidelines not followed; checklist prompts recording of sterile technique and includes option for nurse to answer
“don’t know” if called away emergently; initial infection rate at Johns Hopkins, 11 infections per 1000 patients; implementation
of program reduced rate to zero; rate subsequently dropped in control ICU as well (by implementing similar
procedures); study estimated prevention of 43 CRBSIs and 8 deaths and savings of $2 million
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| Role of technology: human factors key, but need to leverage technology to prevent CRBSI; antibiotic- and antiseptic-
impregnated catheters—meta-analysis found use associated with ≈50% reduction in risk for infection; note—
implement simple techniques (eg, washing hands) before switching to expensive devices
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| Antimicrobial catheters: some prefer antiseptic-coated catheters due to risk for development of resistance with antibiotic-coated
catheters (no known cases, but theoretically possible); study found minocycline/rifampin-coated catheter
more effective than chlorhexidine/silver sulfadiazine-coated catheters (possibly due to biofilm growth); advantages of
antimicrobial-coated catheters include decreases in colonization rates, length-of-stay, and costs
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| Experience at University of California, San Francisco: interventions—hand hygiene (speaker repeatedly reminded
personnel to wash hands; compliance signs also used); central venous catheter insertion checklist; routine use
of US guidance; daily review of antibiotics by pharmacy team and director of infectious disease; daily review of central
venous catheter necessity with prompt removal of unnecessary catheters; ICU discharge preparedness checklist;
compliance—dependent on sharing data; speaker sends monthly compliance report to nurse managers for each ICU
(also places report in nursing lounge and bathroom); sharing data and providing positive feedback and rewards improves
compliance
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| CRBSI reduction: in 2004, 20,000 patient days and 12,000 line days; CRBSI rate, 3.7 infections per 1000 patients, at cost
of $80,000 per CRBSI; 16 deaths expected; after implementation of program, CRBSI rate decreased to 1.7 infections
per 1000 patients, associated mortality decreased by 50%, and estimated $2 million saved
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| Arterial lines: study compared infection rates of peripheral arterial catheters with central venous catheters; 320 arterial
lines in 250 patients; 620 central venous catheters in 410 patients; colonization rate—11% for central lines; 5% for arterial
lines; CRBSI rate—0.3% for arterial catheters; conclusions—actual infection rate from arterial lines extremely
low; speaker does not recommend gown and sterile drape; instead, he suggests using chlorhexidine skin antisepsis (in
place of alcohol swipe) and sterile gloves
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| CURRENT CONCEPTS IN TRANSFUSION MEDICINE —Charles S. Brudney, MB, BCh, Assistant Professor of Anesthesiology,
Duke University School of Medicine, Durham, NC
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| Goals of blood transfusion: increase hemoglobin (Hb) concentration; improve O2 delivery to tissues
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| Transfusion risks: transfusion-transmitted diseases include HIV, hepatitis C, and hepatitis B; relatively low risk for disease
transmission from blood transfusion in United States; other risks include hives, fever, bacterial contamination (particularly
with platelets), immunomodulation, Creutzfeldt-Jakob disease, inflammation, and immunosuppression
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| Immunosuppression: Heiss showed transfusion may enhance tumor recurrence after colorectal cancer resection; Carson
found increased risk for bacterial infection and pneumonia; Vamvakas found prolonged hospital length-of-stay and
increased incidence of infection after coronary artery bypass graft (CABG) surgery
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| Inflammation: transfusion causes induction of HLA antibodies, generation of proinflammatory cytokines, contact activation
with bradykinin release, and passive transfer of donor antibodies (transfusion-related acute lung injury); platelet
transfusions most immunogenic
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| Consequences of prolonged blood storage: corpuscular changes include depletion of adenosine triphosphate
(ATP), decreased 2,3-diphosphoglycerate (DPG), and loss of deformability of red blood cells (RBCs); changes in media
include release of cytokines, bioreactive substances, and free Hb and decreased pH
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| Factors influencing decision to correct anemia: age and cost not considered; factors include cause of bleeding,
ongoing blood loss, metabolic needs, and Hb level; hematocrit—low levels associated with increased mortality
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| Threshold for Hb: study found mortality due to anemia increases with Hb ≤5.0 g/dL and increases dramatically when
Hb <3.0 g/dL; Weiskopf showed Hb ≥5.0 g/dL does not compromise global tissue oxygenation in conscious healthy individuals;
cognitive function impaired at Hb levels between 5.0 g/dL and 6.0 g/dL but reversible with supplemental O2 ;
Hébert study—only multicenter randomized controlled clinical trial of transfusion requirement in clinical care; designed
to compare restrictive (transfused patients with Hb <7.0 g/dL) and liberal (transfused patients with Hb <10.0 g/dL)
strategies for blood transfusion in critically ill euvolemic patients; 30-day and overall mortality rates lower in restrictive
group
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| Transfusion and outcome: prospective observational study in 1999 by Vincent looked at 3500 patients; matched several
variables (eg, Acute Physiology and Chronic Health Enquiry [APACHE-II] score, age, sex, admission type); found
overall mortality rate double for transfused vs nontransfused patients; retrospective study by Engoren reviewed outcomes
of patients who underwent primary CABG; 5-yr mortality rate twice as high in transfused patients as nontransfused patients;
retrospective studies of blood transfusion in patients with acute coronary syndromes reached varying conclusions;
general conclusions—very low Hb harmful; low Hb may be harmful in presence of comorbidity; unnecessary transfusion
may be harmful; best to prevent low Hb
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| Standard of care: American Society of Anesthesiologists (ASA) published guidelines for transfusion therapy in 1996
and 2006; indicated need to “transfuse someone that needs transfusing, and not transfuse someone that doesn’t need
transfusing”; generally accepted; effect of guidelines—Goodnough found guidelines generally not followed unless part
of protocol; conventional laboratory testing too slow; point-of-care testing and protocol-driven therapy necessary to decrease
inappropriate use of products
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| Strategies for blood conservation: preoperative optimization (eg, manage anemia with erythropoietin); aprotinin
and antifibrinolytic therapy; cell salvage; intraoperative autologous donation; adopting new strategies
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| Limiting bleeding: meta-analysis of available therapies by Levi in 1999; treatment with lysine analogues (eg, ε-aminocaproic
acid) or aprotinin decreased bleeding and avoided transfusion; no increase in perioperative MI; aprotinin decreased
mortality 45%, compared with placebo; lysine analogues less effective than aprotinin (likely as effective as
aprotinin in low-risk patients); Mangano stated that association between aprotinin and end-organ damage indicates continued
use not prudent; suggested aprotinin use associated with increased risk for long-term mortality after cardiac surgery;
more recent retrospective database studies show increased risk for mortality among patients undergoing CABG,
and larger increases in serum creatinine levels associated with aprotinin
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| Cell salvage: larger machines used for blood loss of ≥500 mL; washing blood activates factor XII; smaller machines used
for smaller volumes of blood (associated with less factor XII activation) can be attached to drainage tubes after procedure
(may be left in place for 2 days)
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| Autologous normovolemic hemodilution (ANH): remove blood in operating room; give patient crystalloid or colloid
(patient “bleeds more dilute blood”); replace stored blood; technique reduces requirements for RBC transfusion;
ANH has similar efficacy as preoperative autologous donation (PAD) and PAD with erythropoietin; time-consuming
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| Point-of-care testing: intraoperatively, with thromboelastography-guided monitoring or using prothrombin and partial
thromboplastin time, can decrease requirements for transfusion
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| Lowering transfusion trigger: Bracey changed “institutional transfusion trigger” from 9 g/dL to 8 g/dL; resulted in
statistically significant decrease in transfusion rate and no difference in objective or subjective clinical outcomes; saves
resources and cuts cost
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| Relative risk curves: several studies show benefit associated with restrictive transfusion pattern
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Suggested Reading
Berenholtz SM et al: Eliminating catheter-related bloodstream infections in the intensive care unit. Crit Care Med
32:2014, 2004; Bracey AW et al: Lowering the hemoglobin threshold for transfusion in coronary artery bypass procedures:
effect on patient outcome. Transfusion 39:1070, 1999; Darouiche RO et al: A comparison of two antimicrobial-
impregnated central venous catheters. Catheter Study Group. N Engl J Med 340:1, 1999; Dodd RY et al: Current prevalence
and incidence of infectious disease markers and estimated window-period risk in the American Red Cross blood donor
population. Transfusion 42:975, 2002; Engoren MC et al: Effect of blood transfusion on long-term survival after
cardiac operation. Ann Thorac Surg 74:1180, 2002; Hébert PC et al: A multicenter, randomized, controlled clinical
trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical
Care Trials Group. N Engl J Med 340:409, 1999; Erratum in: N Engl J Med 340:1056, 1999; Levi M et al: Pharmacological
strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints. Lancet
354:1940, 1999; McGee DC et al: Preventing complications of central venous catheterization. N Engl J Med
348:1123, 2003; Novotny VM et al: Occurrence of allogeneic HLA and non-HLA antibodies after transfusion of
prestorage filtered platelets and red blood cells: a prospective study. Blood 85:1736, 1995; Pronovost P et al: An intervention
to decrease catheter-related bloodstream infections in the ICU. N Engl J Med 355:2725, 2006; Erratum in: N Engl
J Med 356:2660, 2007; Raad I et al: Central venous catheters coated with minocycline and rifampin for the prevention
of catheter-related colonization and bloodstream infections. A randomized, double-blind trial. The Texas Medical Center
Catheter Study Group. Ann Intern Med 127:267, 1997; Raad I et al: Differential time to positivity: a useful method for
diagnosing catheter-related bloodstream infections. Ann Intern Med 140:18, 2004; Summary for patients in: Ann Intern
Med 140:I39, 2004; Raad I: Intravascular-catheter-related infections. Lancet 351:893, 1998; Rao SV et al: Relationship
of blood transfusion and clinical outcomes in patients with acute coronary syndromes. JAMA 292:1555, 2004; Shore-
Lesserson L et al: Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery.
Anesth Analg 88:312, 1999; Veenstra DL et al: Cost-effectiveness of antiseptic-impregnated central venous catheters
for the prevention of catheter-related bloodstream infection. JAMA 282:554, 1999; Veenstra DL et al: Efficacy of antiseptic-impregnated
central venous catheters in preventing catheter-related bloodstream infection: a meta-analysis. JAMA
281:261, 1999; Vincent JL et al: Anemia and blood transfusion in critically ill patients. JAMA 288:1499, 2002;
Weiskopf RB et al: Acute severe isovolemic anemia impairs cognitive function and memory in humans. Anesthesiology
92:1646, 2000; Weiskopf RB et al: Human cardiovascular and metabolic response to acute, severe isovolemic anemia.
JAMA 279:217, 1998; Erratum in: JAMA 280:1404, 1998.
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