TRANSFUSIONS/EMERGENCIES
| CONTROVERSIES IN NEONATAL AND PEDIATRIC TRANSFUSIONS —Ronald G. Strauss, MD, Professor of Pathology
and Pediatrics, University of Iowa College of Medicine, Iowa City
|
Anemia of Prematurity
| Overview: in early gestation, in utero red blood cell (RBC) production and erythropoiesis inadequate; in late gestation, incomplete
iron transport; after birth, blood drawn for testing; poor erythropoietin (EPO) response to anemia; problem exacerbated
by nutritional difficulties; often requires RBC transfusion
|
| Neonatal hemoglobin (Hb) values in preterm infants: Hb concentration usually high (sometimes lower); drops more
quickly and at 6 to 8 wk of age, nadir 7 to 11 g/dL; then recovery period; at 6 to 7 mo of age (absent chronic problem such
as bronchopulmonary dysplasia), most preterm infants catch up to term infants; early in life, almost no RBC precursors in
marrow (marrow discontinues erythropoiesis); when Hb drops to nadir, burst of erythropoiesis follows; in term infants,
mild physiologic process (does not require transfusions); in preterm infant, problem frequently severe and requires transfusion
|
| Mechanisms: physiologic drop in Hb concentration due to low EPO; phlebotomy losses in sick infants; because of low
EPO levels, inability to respond to anemia and phlebotomy loss; physiologic and pathologic factors—rapid growth of
preterm infant within first several months of life brings commensurate need to increase circulating blood volume, but
child not able to meet it (partially due to low EPO); shortened RBC survival in neonates compared to older children due
to differences in metabolism and membrane structure (problem also partly artifactual); hemolysis and bleeding due to eg,
sepsis or necrotizing enterocolitis (NEC) lowers RBC levels further; patients unable to compensate because of low EPO
and other factors, and RBC transfusion indicated
|
Proposed Guideline for Small-Volume Neonatal Transfusions
| Maintain hematocrit (Hct) per infant’s clinical status: if severe cardiopulmonary problems—Hct target higher
(>35%-45%); moderate cardiopulmonary disease or major surgery—Hct >30%; symptomatic anemia (failure to grow
properly or apneic spells)—once off ventilator, patients transfused at >20% to 25%; speaker’s approach—if no symptoms,
as long as infant feeling fine and growing well, transfusion not needed; most common approach—maintain Hct
≥20%; transfuse regardless of how infant looks
|
| Physiologic indications of RBC status: preferred approach; oxygenation of tissue based on physiologic indications
rather than target Hct; measurement of circulating RBC mass and available O2 delivered to tissues; measurement of O2
delivery and tissue extraction in intensive care; measurement of tissue oxygenation by noninvasive vascular imaging (eg,
near infrared spectral studies)
|
| University of Iowa Health Care (UIHC) RBC transfusion guidelines: if patient ventilated >70% O2 or on extracorporeal
membrane oxygenation—maintain Hct >45%; >40% O2 or sepsis—Hct >39%; <40% O2 or continuous positive
airway pressure—Hct >35%
|
Restricted (Low) vs Liberal (High) RBC Transfusion Thresholds
| Hypothesis: use of restricted transfusion criteria (ie, allowing Hct to fall to lower threshold before initiating transfusion)
should reduce risks of transfusion by reducing number of transfusions, yet avoid undertransfusion
|
| Controlled studies in neonates
|
 | Study from Iowa (Bell et al): infants divided by severity of respiratory disease and transfusion threshold; liberal
threshold—if intubated, once Hct fell to 46%, patients transfused; with improvement or if started at higher level, cutoff
38%; if no respiratory support necessary, Hct cutoff 30%; if restricted—Hct allowed to drop to lower levels for
each phase of clinical stay
|
| Study from Canada: liberal threshold—if cardiorespiratory disease present and patient <1 wk of age, transfusion performed
if Hct 42%; with increasing age, threshold decreased; restricted threshold—transfusion at lower levels; thresholds
based on Hb levels (speaker provided Hct estimates for comparison purposes)
|
| Number of transfusions: in both studies, statistically fewer transfusions per infant if restricted threshold used
|
| Outcomes: no statistically significant difference between liberal and restricted groups—in rates of mortality, bronchopulmonary
dysplasia, patent ductus arteriosus, or retinopathy of prematurity; growth rates and O2 needs also similar; alarming
difference—in Iowa study, restricted group had more apnea and central nervous system (CNS) injury; all periventricular
leukomalacia and grade IV intraventricular hemorrhages occurred in restricted group; controversial (Canadian study did not
replicate such findings); further study needed (speaker supports current more liberal approach in interim)
|
More Research on Infants and Neonates
| Delayed cord clamp at time of birth protects CNS from bleeding (Mercer et al): delayed cord clamping ≈1 min allows
transfusion of placental blood (≈20 mL/kg) to increase tissue perfusion at time of birth; if cord clamping delayed up
to 45 sec, rate of intraventricular hemorrhage only 14% (5/36 infants) vs 36% with immediate clamping
|
| Brain injury and decreased CNS oxygenation (Kissack et al): if CNS injury present, cerebral fractional oxygen extraction
variable but increased markedly at time of CNS bleeding; suggests that if insufficient O2 supplied to brain, low
pretransfusion Hct may place infants at risk for CNS injury; speaker’s approach—transfuse infants according to usual
guidelines until more known; alternative view—Canadians strong advocates for restricted transfusion programs
|
RBC Transfusion in Older Children (Overview)
| Goals: if bleeding >25% of blood volume—under most guidelines, giving RBCs appropriate; if percentage less, crystalloid
or colloid acceptable (person with normal hematopoiesis will recover RBCs in time); increased O2 delivery to
tissues—seen in patient with chronic anemia, or slow or intermittent bleeding, or after bleeding controlled in trauma or
surgery, or hematologic disease (insufficient RBC production or hemolytic process); small-volume transfusion (10 mL/
kg) increases Hb from 1.0 to 1.5 g/dL; avoid being wasteful of blood left in bag, but also avoid overloading child
|
| Guidelines: consider RBC transfusion if Hb ≤7 g/dL (Hct 21%), and heart, lung, kidney, CNS, and marrow function adequate
(if function impaired, some transfuse at higher level); in perioperative and critical care setting—transfuse at Hb
concentration ≤8 g/dL (anticipates bleeding and stress of surgery); severe cardiopulmonary disease—≤11 g/dL; marrow
or renal failure with severe thrombocytopenia—≤10 g/dL; goal to avoid stem cell competition in marrow; platelets work
better if Hct ≈30%; if child thrombocytopenic, transfusing platelets and RBCs may be indicated
|
| Adverse effects of RBC storage: RBCs undergo metabolic and morphologic changes (problem of rigidity and development
of echinocytes and schistocytes); recent studies suggest blood stored longer than 15 to 21 days associated with decreased
tissue perfusion and increased morbidity and mortality; controversial (currently, blood stored up to 42 days);
more data needed; speaker’s approach—pending further study, continue to transfuse using current practices
|
Cardiac Toxicity of Potassium (K+) with Rapid Infusion
| Overview: risk depends on dose and rate of infusion (not necessarily K+ concentration); patient factors—plasma K+ level
pretransfusion; overall body water K+ (patient chronically K+ depleted?); total body K+ (almost all K+ within cells, not
fluids; fluctuation with infusion)
|
| Potassium requirement and replacement: normal maintenance therapy 1 to 3 mEq/kg per day; most intravenous fluids
contain 20 to 40 mEq/L; RBC changes during storage—due to cold temperature, sodium-potassium (Na+/K+) ATPase
pump shuts down and K+ leaks into “plasma” (extracellular fluid); at 42 days, K+ concentration 50 to 60 mEq/L
|
| K+ dose of 42-day RBCs in infants: in these patients, K+ concentration high; give 15 mL/kg transfusion at 60% Hct; if
K+ content 50 mEq/L, transfusion 9 mL RBCs, 6 mL plasma with 0.3 mEq/kg K+; speaker frequently infuses small-volume
transfusions to infants over 3- to 4-hr period; recent studies show K+ not issue for tiniest preterm infants when small-
volume transfusions given slowly; use of single unit creates reserve for infant and avoids donor exposures
|
| Rapid transfusion of stored RBCs in older children: at 42 days, “plasma” K+ 50 mEq/L; RBC unit volume 300 mL
(190 mL packed RBCs, 110 mL of plasma [residual from when transfused], and 100 mL of preservative media); at this volume,
5.5 mEq K+ in 110 mL plasma (0.05 mEq/mL), or 300 mL RBCs (0.02 mEq/mL of combined RBCs and plasma); replacement
K+ 0.002 mEq/kg per minute; for rapid infusion, probably double to 0.004 mEq/kg per minute; storage ≤7 days—
fresh RBCs; infuse 1.0 mL/kg per minute; 20 to 22 days—usual age of RBCs; infuse 0.4 mL/kg per minute; 42 days—oldest
RBCs; cut rate in half to 0.2 mL/kg per minute; unless RBCs known to be fresh, use average age for calculation (do not exceed
0.5 mL/kg per minute)
|
| Resuscitation of bleeding children: logic suggests using same rules as for older patients; try to restore volume with nonblood
fluids (eg, crystalloid, saline, Ringer’s lactate, albumin solution); give RBCs at safe doses and rates to maintain Hct
≥24%; if giving fresh RBCs—do not exceed 1 mL/kg per minute; stored RBCs—if age of blood unknown, use average age
(20-22 days) for estimate; give at half rate (eg, 0.5 mL/kg per minute in infant); reason—children have died from cardiac arrest
after receiving older RBCs at rapid rate because K+ level too high
|
| LESSSONS LEARNED FROM THE PEDIATRIC EMERGENCY DEPARTMENT —Jane F. Knapp, MD, Professor and
Vice Chair of Pediatrics, University of Missouri School of Medicine, and Director of Graduate Medical Education, Children’s
Mercy Hospital, Kansas City, MO
|
Back Pain
| Case 1: 4-yr-old girl presented to emergency department (ED) with 6-mo history of intermittent low back pain that had
worsened over past several weeks; over past 48 hr, dramatic change; child developed unsteady gait and urinary incontinence;
children vs adults—back pain less common in children but more likely to signify pathology; source usually not
ruptured disc, osteoarthritis, or significant back spasms; diagnosis often difficult because children less able to describe
and localize pain; back pain in children meaningful until proven otherwise (perform thorough history and physical examination);
physical examination—dramatic bilateral hyperreflexia and decreased muscle strength in lower extremities;
normal sensation and proprioception; magnetic resonance imaging (MRI) shows extradural mass causing compression of
cervical spinal cord; computed tomography (CT) of brain shows fourth-ventricle mass; in this case, nonobstructive
(therefore, no headache or vomiting); diagnosis, germ cell tumor
|
| Spinal cord compression: neurosurgical emergency; tumors one cause; pain most important symptom (worse when supine;
localized in thoracic region); tap spinous processes to detect tenderness to percussion; muscle weakness and loss of
bowel or bladder function late findings; treatment begins with dexamethasone to decrease inflammation; immediate neurosurgical
consult indicated
|
| Case 2: 13-yr-old girl presented to pediatrician with history of hyper-IgE syndrome, asthma, eczematous rash, and 3-wk
history of low back pain; symptomatic treatment recommended and patient sent home; over time, pain worsened and patient
developed intermittent fever and difficulty walking; family suspected malingering; back pain in adolescents—do
not assume adult-type cause for back pain; psychogenic back pain diagnosed with caution; frequent school absences may
be clue to school avoidance; ask about family dynamics; back pain with limp puts spinal cord involvement in differential
diagnosis; look for injuries due to stress or overuse, especially in athletes; case 2 continued—in ED, patient diagnosed
with pneumonia, started on oral antibiotics, and sent home; blood cultures positive for methicillin-resistant Staphylococcus
aureus (MRSA) and methicillin-sensitive S aureus (MSSA); infectious complications—lung abscess adjacent to
paraspinous abscess, which is contiguous with epidural abscess and to osteomyelitis of spine
|
| Serious causes of back pain in children: neoplastic (eg, case 1), infectious (eg, case 2), and traumatic; trauma usually
presents with associated history; patients with muscle spasm or injury tend to have paraspinous muscle spasm that can be
localized, but not tenderness with percussion over spinous processes; these patients respond to nonsteroidal anti-inflammatory
drugs and improve with time; on physical examination, look for localized tenderness over spine; if found, infectious
process may be present aside from, or in addition to, eg, pneumonia
|
Ear Drainage
| Case 3: 7-yr-old boy poked in right ear with incense stick, and ear began draining clear fluid; patient became dizzy and
started bumping into things and vomiting; in ED, patient diagnosed with otitis media and started on antibiotics; ear drainage
and vomiting continued; after 2 days, primary care physician administered intramuscular penicillin; drainage continued
and patient returned to ED; on presentation, large fluid-soaked gauze pad on right shoulder and continuous stream of
fluid dripping from ear; CT of brain showed pneumocephalus in cochlea of inner ear; exploration of ear showed footplate
of stapes shattered, perforating oval window and allowing air to enter cochlea and inner ear; fluid identified as cerebrospinal
fluid; injury caused patient to develop meningitis
|
Nasal Septal Hematoma
| Case 4: 11-yr-old boy hit in nose twice in same day, with subsequent bleeding in both instances; next day, patient developed
fever; initial diagnosis viral infection; 2 days later, nose swollen and patient taken to ED, but not treated; next day,
on return to ED, patient diagnosed with poison ivy and started on antihistamine and prednisone; elevated temperature and
nasal swelling persisted, and patient returned to ED; on examination, bilateral nasal septal hematomas recognized (left
nostril occluded; in right nostril, slight rim allowing air and fluid to enter)
|
| Reasons for delayed diagnosis: failure to examine nose or failure to recognize nasal findings
|
| Complications: absorption of nasal cartilage and subsequent saddle deformity; infection (patients at risk for cavernous sinus
thrombosis); perforation; nasal obstruction
|
| Diagnosis and treatment: in children, problem tends to be bilateral; hematoma drained surgically in operating room under
sterile conditions; antibiotics used to treat or prevent infection
|
Bruising in Infants
| Case 5: 4-mo-old infant presented with facial bruising; parents reported that 2-yr-old sibling hit him with toy truck; on examination,
bruise not focal over bony prominence but spread out and possible appearance of hand print
|
| Bruises and abuse: relate bruising to age and developmental stage; compare location and pattern to history; no good studies
to show that bruises can be dated accurately
|
| “Children who don’t cruise rarely bruise”(Sugar et al): subjects <36 mo of age; pediatricians documented presence,
location, and potential causes of bruises; in children <6 mo of age, only 2/366 had bruises (0.6%); in children <9 mo of
age, rate 1.7%; bruising very unusual before infant able to cruise (ie, walking with support); in this study, cruising began
at 9 mo of age; 18% of cruisers had bruises; 52% of walkers had bruises
|
Suggested Reading
Bell EF et al: Randomized trial of liberal versus restrictive guidelines for red blood cell transfusion in preterm infants. Pediatrics
115:1685, 2005; Jenny C et al: Analysis of missed cases of abusive head trauma. JAMA 281:621, 1999; Kirpalani
H et al: The Premature Infant in Need of Transfusion (PINT) study: a randomized, controlled trial of a restrictive
(low) versus liberal (high) transfusion threshold for extremely low birthweight infants. J Pediatr 149:301, 2006; Kissack
CM et al: Postnatal changes in cerebral oxygen extraction in the preterm infant are associated with intraventricular hemorrhage
and hemorrhagic parenchymal infarction but not periventricular leukomalacia. Pediatr Res 56:111, 2004; Lacroix J
et al: Transfusion strategies for patients in pediatric intensive care units. N Engl J Med 356:1667, 2007; Mercer JS et al:
Delayed cord clamping in very preterm infants reduces the incidence of intraventricular hemorrhage and late-onset sepsis: a
randomized, controlled trial. Pediatrics 117:235, 2006; Miller MA, Schlueter AJ: Transfusions via hand-held syringes
and small-gauge needles as risk factors for hyperkalemia. Transfusion 44:373, 2004; Seidel JS, Knapp JF: Pediatric
emergencies in the office, hospital, and community: organizing systems of care. Pediatrics 106:337, 2000; Strauss RG et
al: Circulating RBC volume, measured with biotinylated RBCs, is superior to the Hct to document the hematologic effects
of delayed versus immediate umbilical cord clamping in preterm neonates. Transfusion 43:1168, 2003; Strauss RG: Controversies
in the management of the anemia of prematurity using single-donor red blood cell transfusions and/or recombinant
erythropoietin. Transfus Med Rev 20:34, 2006; Sugar NF et al: Bruises in infants and toddlers: those who don’t
cruise rarely bruise. Puget Sound Pediatric Research Network. Arch Pediatr Adolesc Med 153:399, 1999.
Cultural and Linguistic Resources
In compliance with California Assembly Bill 1195, Audio-Digest Foundation offers selected cultural and linguistic resources
on its website. Please visit this site: www.audiodigest.org/ CLCresources.
Educational Objectives
| The goal of this program is to improve transfusion practices and emergency care in pediatric patients. After hearing and assimilating
this program, the clinician will be better able to:
|
| 1. Perform blood transfusions in infants safely and effectively.
|
| 2. Follow current guidelines for transfusions in older children.
|
| 3. Interpret recent findings about the safety and efficacy of using restrictive transfusion thresholds.
|
| 4. Diagnose and manage spinal cord compression.
|
| 5. Recognize bruising in infants as a red flag for possible child abuse.
|
Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members 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 faculty reported nothing to disclose.
Acknowledgements
Dr. Strauss was recorded at the 8th Annual Southwest Pediatric and Neonatal Hematology/Oncology for the Practitioner,
presented August 19, 2006, in Albuquerque, NM, by the University of New Mexico Health Sciences Center School of Medicine,
Department of Pediatrics, and the Office of Continuing Medical Education; Dr. Knapp was recorded at the 39th Annual
Advances and Controversies in Clinical Pediatrics, presented June 1-3, 2006, in San Francisco by the Department of
Pediatrics, University of California, San Francisco, School of Medicine. The Audio-Digest Foundation thanks Drs. Strauss
and Knapp, and the meeting sponsors, for their cooperation in the production of this program.
|
