There is evidence to support that pain and distress does not decrease with repeated procedures and may worsen if pain is not adequately managed.1,2 In 1990, the first recommendations on the management of pain and anxiety associated with procedures for children with cancer were published by the American Academy of Pediatrics.1 Guiding principles described in the recommendations continue to hold true today:
- Maximize comfort and minimize pain. The ideal goal for procedure pain management is to make the experience as comfortable as possible for the child and parents.
- Use nonpharmacologic and pharmacologic interventions. Nonpharmacologic interventions like cognitive-behavioral interventions (CBI) should be taught to every child who is developmentally able to use these strategies to decrease anxiety and distress. Pharmacologic therapies are safe and effective when carefully administered and monitored by appropriately trained personnel.
- Prepare the child and family. The key to managing procedure-related pain and distress is preparation and education. Parents and children should receive appropriate information regarding what to expect before, during, and after the procedure. Stress reducing techniques can be taught for use before, during, and after procedures.
- Consider the developmental age of the child. The child's cognitive development provides the foundation for establishing standards of care for children undergoing painful procedures.
- Support family and child involvement. Families should be involved in choices offered for pharmacologic and nonpharmacologic therapies.
- Assure provider competency in performing procedures and sedation. Procedures must be performed by persons with technical expertise or by providers directly supervised by experts.
- Use appropriate monitoring to assure safety. Sedation and anesthesia should be administered in a monitored setting with immediately available resuscitative drugs and equipment.3
Key components to managing painful procedures in children with cancer include effective parent teaching and education, appropriate preparation for the procedure for both parent and child, and optimal analgesia and sedation. This article provides a review of child and family preparation for painful procedures and a review of the latest pharmacological and nonpharmacological interventions most effective in minimizing pain and discomfort.
CHILD AND FAMILY PREPARATION FOR PROCEDURES
Children and their families should be prepared before the procedure and well supported during and after painful procedures.4,5 By first establishing rapport with the child and family, the clinician is able to assess the family's knowledge of the procedure, expectations, and preferred learning style.5 This assessment should include discussion of the child's developmental level, coping strategies, and previous experiences with procedures that can greatly impact his/her anxiety level.2,4 Table 1 provides a developmental overview of important aspects to consider when preparing children of all ages and their families for painful procedures.
Inclusion of child life programs in pediatric settings has become widely accepted and advocated by the American Academy of Pediatrics.6 With expertise in child development, child life specialists (CLS) promote effective coping and adjustment during potentially stressful situations through play, psychological preparation, education, and support. CLS prepare children psychologically for medical procedures and events to increase their sense of mastery, reduce anxiety, and plan and rehearse coping strategies. Psychological preparation is patient focused and is defined as a “process of communicating accurate and developmentally appropriate information, identifying potential stressors, as well as planning and practicing coping strategies.”6
Whether taught by a CLS or nurse, educational preparation for the procedure emphasizes sensory aspects of the procedure: what the child will feel, see, hear, smell, and touch and what the child can do during the procedure (eg, lie still, count out loud, squeeze a hand, hug a doll). Allow for ample discussion during educational preparation to prevent information overload and confusion and ensure satisfactory feedback. Allow the child to practice procedures and be comfortable with the sequence of events that will require cooperation (eg, deep breathing). Teaching dolls are frequently used to help children understand where on the body the procedure will be performed. Allowing the child choices when possible and empowering the child by giving them specific roles or jobs during the procedure decreases fear and anxiety. Emphasize that the procedure will end quickly and stress any pleasurable events afterward (eg, going home, seeing parents). Provide a positive ending, praising efforts at cooperation and coping.
Like the child, parents also experience high levels of stress during procedures, and their anxiety does not decrease during treatment. However, parent anxiety levels can be minimized when the child is adequately prepared.7–9 Several studies report a positive impact on parental distress and satisfaction and no difference in technical complications when parents remain with children.8,10,11
CBI are techniques intended to alter the procedure experience by changing the child's thoughts through attention diversion, images, and self-determination.1,2,7,11–19 Examples of common CBI strategies used with children with cancer include distraction through music or other pleasant diversions, story telling, deep breathing, relaxation, guided imagery, massage, and yoga. CBI techniques are known to decrease anxiety and discomfort during painful procedures 1,2,12–19 and a variety of techniques are available to facilitate the child and family's coping during the procedure (Table 2). Distraction involves concentrating on an event or object other than the pain. Distraction is a powerful coping strategy during painful procedures.20 Infants and toddlers are easily distracted because of their short attention span. Distraction is accomplished by focusing the child's attention on something other than the procedure. Singing favorite songs, listening to music with a headset, counting aloud, or blowing on a magic wand are effective techniques.
Older children can be distracted with activities such as video games, television, and music. Guided imagery works well with school-aged children and adolescents who can visualize an enjoyable experience or pleasant memory. The child describes the event in detail as he or she visualizes it. The child describes details of the event, including as many senses as possible (eg, “feel the cool breezes,” “see the beautiful colors,” “hear the pleasant music”). The child concentrates only on the pleasurable event during the painful time by enhancing the image, often by reading a script or playing a tape. The effectiveness of this method is enhanced by the use of a coach. The coach may be a parent or other adult who discusses the event with the child and keeps the image alive during the procedure. Muscle relaxation is another CBI that is useful in children and adolescents. The child is asked to take a deep breath and “go limp as a rag doll” while exhaling slowly; then ask child to yawn. Begin progressive relaxation by starting with the toes, and systematically instructing the child to let each body part “go limp” or “feel heavy”; if child has difficulty relaxing, instruct child to tense or tighten each body part and then relax it. The child can keep eyes open, as children may respond better if eyes are open rather than closed during relaxation.
As parent participation plays a major role in reducing a child's anxiety associated with procedures,4,5 when possible, parents should have the option to remain with their child during the procedure and be involved in the CBI techniques used.
SEDATION FOR PROCEDURES
There are 3 main categories of sedation used for painful procedures: minimal sedation, moderate sedation, and deep sedation/general anesthesia. CBI should be used in combination with sedation/analgesic agents. Table 3 provides a brief description of each sedation category.
Children receiving minimal sedation are able to respond to verbal commands; airway, spontaneous ventilation, and cardiovascular function are unaffected.3 This type of sedation is achieved by administering agents to treat symptoms of anxiety (Table 4). The benefits of anxiolytic therapy should be carefully considered as there are side effects including paradoxical effects resulting in agitation. It remains important to work with each child, using CBI during their procedure so they develop coping skills over time. Once the child's anxiety lessens, nonpharmacologic interventions may become sufficient and anxiolytics may no longer be needed.
Moderate sedation is a drug-induced depression of consciousness during which the patient responds purposefully to verbal command, either alone or accompanied by light tactile stimulation.3 Usually no interventions are necessary to maintain a patent airway. Spontaneous ventilation is adequate and cardiovascular function is maintained. Numerous studies report midazolam, fentanyl, and ketamine as safe and effective agents for moderate sedation for painful procedures in children with cancer (Table 5).22–29 Two agents are often combined to provide both sedation and analgesia. Ketamine, fentanyl, and midazolam can be administered by a nonanesthesiologist outside of the operating room when proper monitoring and trained personnel are available.7,24–27,29–32 It is essential to continue using CBI with these children to develop coping skills over time, even when moderate sedation is used.
Midazolam is a benzodiazepine with no analgesic properties of its own. Fentanyl is an opioid analgesic, and ketamine is a dissociative anesthetic/analgesic. These drugs are administered in combination to provide both sedation and analgesia. However, combining midazolam and ketamine in some childhood cancer patients is associated with hypoxia, hypertension, tachypnea, vomiting, and hallucinations.25,28,29 Combining midazolam and fentanyl may cause decreased heart rate and blood pressure, oxygen desaturation, and emesis.24 Administering ondansetron with the analgesia agents reduces vomiting or retching after the procedure.30
The risk for ketamine complications is dose and age dependent. In a 2009 meta-analysis on emergency department procedural sedation, ketamine caused increased airway or respiratory adverse events, emesis, and recovery agitation when administered in an unusually high intravenous dose (initial dose ≥2.5 mg/kg or total dose ≥5.0 mg/kg).22,23 Ketamine was associated with adverse airway and respiratory events in children younger than 2 years and those 13 years and older, as well as increased emesis in younger adolescents. Older children have less distress with procedures than younger children when moderate sedation is used.7,33 Distress is further reduced by adding nonpharmacologic interventions to the sedation drug regimen.7,32,34–37
Nitrous oxide (N2O) is an anesthetic gas that provides moderate sedation and is most commonly used for painful dental procedures in children.38,39 In a small number of studies, N2O was effective in reducing pain and anxiety in children undergoing various painful nondental procedures [eg, venous cannulation, lumbar puncture (LP), bone marrow aspiration (BMA), and dressing change].40–42 In these studies, concentrations of N2O varied (ranging from 0% to 70% N2O in oxygen) and were administered by certified nurses or physicians in a controlled setting such as a clinic, procedure room, or operating room. Patients who received N2O before procedures had lower levels of distress, lower pain scores, were more relaxed, and many had no recollection of the procedure.40–42
A small percentage of patients (ranging from 5% to 15%) experienced minor side effects from N2O; the most common included nausea, vomiting, excitement, dysphoria, and oxygen desaturation.40,41 More serious complications such as inhibition of the methionine pathway, hematological, neurological, and/or myocardial injury were associated with prolonged N2O use (>6 h) and higher concentrations (>70% N2O in oxygen).43 Serious side effects are not found in the review of studies using N2O for procedures that involve short-term sedation. Adequate room ventilation and effective scavenging systems are required when using N2O to reduce exposure to ambient gas.39,44,45 In addition, the N2O system must be capable of administering 100% oxygen (never <30% oxygen), and be regularly checked and calibrated.39,44
Dexmedetomidine has also received recent attention as a moderate sedation agent. Dexmedetomidine, an α-2 agonist with analgesic properties that control stress, anxiety, and pain, is effective as a single agent for sedation for noninvasive procedures and is used most often for lengthy radiological imaging such as magnetic resonance imaging.46–50 However, when used alone it does not provide deep enough sedation to be beneficial for painful procedures such as BMA or LP.
Deep sedation is a drug-induced depression of consciousness when the child cannot be easily aroused but responds purposefully after repeated or painful stimulation. Medications used for moderate sedation can cause deep sedation and the trained sedation specialist should be able to manage any complications as the ability to independently maintain ventilatory function may be impaired. Children may require assistance in maintaining a patent airway, and spontaneous ventilation may be inadequate. Cardiovascular function is usually maintained.3
General anesthesia is a drug-induced loss of consciousness when the child is not arousable, even by painful stimulation. Children often require assistance in maintaining an airway, and positive pressure ventilation is often used because of depressed spontaneous ventilation or drug-induced depression of neuromuscular function. Cardiovascular function may be impaired.3
Propofol, a short-acting sedative hypnotic, is one of the most widely used agents for brief invasive procedures preformed on children with cancer. It is administered intravenously either by continuous infusion or intermittent boluses (Table 5). Propofol, when administered slowly over at least 1 minute, provides rapid anesthesia induction, amnesia; during recovery this agent causes less agitation and has a lower incidence of nausea and vomiting.51,52 Propofol has no analgesic properties and short-acting opioids such as fentanyl may be used in combination to alleviate pain. The addition of an analgesic agent such as fentanyl can result in lower propofol doses (median 3.1 mg/kg vs. 4.6 mg/kg), fewer adverse effects (18% vs. 50%), and a shorter recovery period (37 min vs. 26 min).53–55 When remifentanil, an ultra-short-acting opioid, was used in combination with propofol in 80 children undergoing BMAs, it allowed for an overall propofol dose reduction and decreased time to discharge, but it increased the risk of respiratory depression.56
Whether used alone or in combination, propofol can cause apnea, hypotension, and airway obstruction. Therefore, this agent must be administered in a controlled setting with experienced personnel trained in advanced airway management skills with resuscitative equipment readily available.9,21,33,51,52,55,57,58
HOW TO CHOOSE THE SEDATION CATEGORY
There are several choices for sedation that can be administered in outpatient and inpatient cancer settings. Minimal sedation can be safely administered in the clinic or an inpatient unit. Moderate and deep sedation can also be administered in similar areas, but require the immediate availability of resuscitation drugs and equipment and trained personnel who are competent in airway management and sedation.
General anesthesia is administered by anesthesiologists in the operating room and sites outside the operating room specifically established for safe delivery of general anesthetics.
Practitioners administering sedative agents and monitoring patients should have documented sedation competency. For all patients receiving moderate deep sedation, recommended monitoring includes continuous pulse oximetry, observation of ventilation, and blood pressure measurement. For patients whose ventilation cannot be observed directly during moderate or deep sedation, either exhaled/end-tidal carbon dioxide can be monitored or capnography can be used. Level of consciousness should be assessed at regular intervals throughout the sedation process. During deep sedation, practitioners must be proficient in airway management and advanced life support to rescue patients from a deeper level of sedation than intended to reduce the risk of hypoxia, hypoventilation, and hypotension. Advanced life support equipment must be immediately accessible and supplemental oxygen should be administered unless contraindicated.
The American Society of Anesthesiologists describes monitored anesthesia care as an assortment of postprocedure responsibilities, beyond the expertise of practitioners providing moderate sedation, that assures a return to full consciousness, relief of pain, management of adverse physiological responses, or side effects from medications administered during the procedure, while considering coexisting medical problems.59 A clinical algorithm developed to guide the decision making process for the type of sedation based on the specific procedure is found in Figure 1. Considerations for deep sedation or general anesthesia should include the:
- Type of procedure
- Length of procedure
- Number of procedures
- Newly diagnosed oncology patients
- Downs syndrome/cognitively impaired patients
- Patients who had problems with procedures or obtaining adequate sedation in the clinic or inpatient setting
- Patients with allergic reactions to sedative medications
- Patients with medical conditions requiring an anesthesiologist to administer sedation or general anesthesia.
Any child with unusual circumstances should be discussed with an anesthesiologist before determining the type of sedation. Children at risk for difficult airways may include morbidly obese patients (body mass index ≥35) and patients with craniofacial anomalies (eg, Treacher-Collins, Pierre Robin) and patients with mucopolysaccharidoses (eg, Hurler, Hunter, Morquio). It is recommended that the following types of patients be managed by an anesthesiologist in the operating room:
- Infants <6 months of age
- Patients who have an oxygen requirement
- Patients in shock, hypotensive, impending septic shock (eg, patients with high fevers and unstable volume status requiring fluid boluses on the day of the procedure)
BMA and Biopsy
When possible, all first time BMAs and biopsies should be performed under deep sedation or general anesthesia, regardless of age. As children do not habituate to this painful procedure, deep sedation/general anesthesia is recommended for all bone marrow biopsies. However, there are selected children who can undergo BMA without sedation, and each child's management should be individualized. A local anesthetic using 1% buffered-lidocaine should always be used for the BMA and biopsy. The use of a local anesthetic, when carried out properly is key to minimizing discomfort (Table 6).
Children receiving frequent LPs during the first few months of cancer therapy may require sedation. Options for having LPs performed without sedation should be discussed with the parents and child after the initial diagnostic period. A topical anesthetic should be used for all LPs, especially when sedation is not administered. For children with suspected leukemia, a practitioner experienced at procedures should perform the first diagnostic LP, as well as the first procedure in which the patient is transitioning from moderate to minimal sedation. Deep sedation or general anesthesia should always be considered for children undergoing more than one procedure (eg, both BMA and LP).
Although significant advances in procedure management have been made in the last 25 years since the days of chloral hydrate and the demoral, phenergan and thorazine cocktail, there remains a continued need to explore more effective agents that provide short-term sedation with minimal side effects. There is limited research on the use of newer agents such as remifentanyl, a short-acting opioid, or short-term sedation with agents such as N2O. Continued use of CBI for all children should be a standard of care and creative interventions developed and tested to increase children's coping skills are still needed.
The guiding principles established 20 years ago for effectively managing painful procedures in children with cancer hold true today.1 Essential components for a procedure management program must include effective parent teaching and education, procedure preparation for both parent and child, and appropriate analgesia and sedation. Although new and better pharmacologic agents now exist, management of painful procedures in children with cancer must be tailored to the individual patient by effective communication between the child, parents, and medical staff of successful multimodal interventions.
1. Zeltzer LK, Altman A, Cohen DL, et al. Report of the subcommittee on the management of pain associated with procedures in children with cancer. Pediatrics.. 1990;86:826–831.
2. Katz ER, Kellerman J, Siegel SE.. Behavioral distress in children with cancer undergoing medical procedures: developmental considerations. J Consult Clin Psychol.. 1980;;48::356–365.
4. Dahlquist LM, Power TG, Cox CN, et al. Parenting and child distress during cancer procedures: a multidimensional assessment. Child Health Care.. 1994;23:149–166.
6. American Academy of Pediatrics. . Committee on Hospital Care. Child life services. Pediatrics.. 2006;118:1757–1763.
7. Kazak AE, Penati B, Brophy P, et al. Pharmacologic and psychologic interventions for procedural pain. Pediatrics.. 1998;102:59–66.
8. Cline R, Harper F, Penner L, et al. Parent communication and child pain and distress during painful pediatric cancer treatments. Soc Sci Med.. 2006;63:883–898.
9. Crock C, Olsson C, Phillips R, et al. General anaesthesia or conscious sedation for painful procedures in childhood cancer: the family's perspective. Arch Dis Child.. 2003;88:253–257.
10. Piira T, Sugiura T, Champion GD.. The role of parental presence in the context of children's medical procedures: a systematic review. Child Care Health Dev.. 2005;31:233–243.
11. Christensen J, Fatchett D.. Promoting parental use of distraction and relaxation in pediatric oncology patients during invasive procedures. J Pediatr Oncol Nurs.. 2002;19:127–132.
12. Blount RL, Sturges JW, Powers SW.. Analysis of child and adult behavioral variations by phase of medical procedure. Behav Ther.. 1990;21:33–48.
13. Ellis JA, Spanos NP. Cognitive-behavioral interventions for children's distress during bone marrow aspirations and lumbar punctures: a critical review J Pain Symptom Manage.. 1994;9:96–108
14. McCarthy AM, Cool VA, Hanrahan K. Cognitive behavioral interventions for children during painful procedures: research challenges and program development J Pediatr Nurs.. 1998;13:55–63
15. Chen E, Joseph MH, Zeltzer LK. Behavioral and cognitive interventions in the treatment of pain in children Pediatr Clin North Am.. 2000;47:513–525
16. FavaraScacco C, Smirne G, Schiliró G, et al. Art therapy as support for children with leukemia during painful procedures Med Pediatr Oncol.. 2001;36:474–480
17. Dahlquist LM, Busby SM, Slifer KJ, et al. Distraction for children of different ages who undergo repeated needle sticks J Pediatr Oncol Nurs.. 2002;19:22–34
18. Kuppenheimer WG, Brown RT. Painful procedures in pediatric cancer: a comparison of interventions Clin Psychol Rev.. 2002;22:753–786
19. Kwekkeboom KL. Music versus distraction for procedural pain and anxiety in patients with cancer Oncol Nurs Forum.. 2003;30:433–440
20. Uman LS, Chambers CT, McGrath PJ. Psychological interventions for needle-related procedural pain and distress in children and adolescents Cochrane Database Syst Rev.. 2006;4:CD005179. Review.
21. Holdsworth M, Ralsch D, Winter S, et al. Pain and distress from bone marrow aspirations and lumbar punctures Ann Pharmacother. 2003;37:17–22
22. Green SM, Roback MG, Krauss B, et al. Predictors of airway and respiratory adverse events with ketamine sedation in the emergency department: an individual-patient data meta-analysis of 8282 children Ann Emerg Med. 2009;54:158–168
23. Green SM, Roback MG, Krauss B, et al. Predictors of emesis and recovery agitation with emergency department ketamine sedation: an individual-patient data meta-analysis of 8282 children Ann Emerg Med. 2009;54:171–180
24. Mantadakis E, Katzilakis N, Foundoulaki E, et al. Moderate intravenous sedation with fentanyl and midazolam for invasive procedures in children with acute lymphoblastic leukemia J Pediatr Oncol Nurs. 2009;26:217–222
25. Bhatnagar S, Mishra S, Gupta M, et al. Efficacy and safety of a mixture of ketamine, midazolam and atropine for procedural sedation in paediatric oncology: a randomised study of oral versus intramuscular route J Paediatr Child Health.. 2008;44:201–204
26. Evans D, Turnham L, Barbour K, et al. Intravenous ketamine sedation for painful oncology procedures Paediatr Anaesth. 2005;15:131–138
27. Meyer S, Aliani S, Graf N, et al. Inter- and intraindividual variability in ketamine dosage in repetitive invasive procedures in children with malignancies Pediatr Hematol Oncol.. 2004;21:161–166
28. Pellier I, Monrigal JP, Le Moine P, et al. Use of intravenous ketamine-midazolam association for pain procedures in children with cancer. A prospective study Paediatr Anaesth. 1999;9:61–68
29. Marx CM, Stein J, Tyler MK, et al. Ketamine-midazolam versus meperidine-midazolam for painful procedures in pediatric oncology patients J Clin Oncol. 1997;15:94–102
30. Nagel K, Willan AR, Lappan J, et al. Pediatric oncology sedation trial (POST): a double-blind randomized study Pediatr Blood Cancer.. 2008;51:634–638
31. Ljungman G, Kreuger A, Andréasson S, et al. Midazolam nasal spray reduces procedural anxiety in children Pediatrics. 2000;105:73–78
32. Hedén L, von Essen L, Frykholm P, et al. Low-dose oral midazolam reduces fear and distress during needle procedures in children with cancer Pediatr Blood Cancer. 2009;53:1200–1204
33. Ljungman G, Gordh T, Sorensen S, et al. Lumbar puncture in pediatric oncology: conscious sedation versus general anesthesia Med Pediatr Oncol.. 2001;36:372–379
34. American Academy of Pediatrics Committee on Drugs. . Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures Pediatrics. 1992;89:1110–1115
35. Cote CJ, Wilson S. Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures: an update Pediatrics. 2006;118:2587–2602
36. Cote CJ, Wilson SWork Group on Sedation. . Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures: an update Paediatr Anaesth. 2008;18:9–10
37. Committee on Drugs and Psychosocial Aspects of Child and Family Health. . . The assessment and management of acute pain in infants, children, and adolescents. Pediatrics. 2001;108:793
38. Quarnstrom FC, Mar RS. A premix of 50% nitrous oxide—50% oxygen for sedation during dental procedures Anesth Prog.. 1983;30:197–198
39. Howard WR. Nitrous oxide in the dental environment: assessing the risk, reducing the exposure J Am Dent Assoc. 1997;128:356–360
40. Henderson JM, Spence DG, Komocar LM, et al. Administration of nitrous oxide to pediatric patients provides analgesia for venous cannulation Anesthesiology. 1990;72:269–271
41. Kanagasundaram SA, Lane LJ, Cavalletto BP, et al. Efficacy and safety of nitrous oxide in alleviating pain and anxiety during painful procedures Arch Dis Child.. 2001;84:492–495
42. Slagerman K, Livingston M. (2008, September 27, 2008). Nurse-directed program to assess patient/parent satisfaction using nitrous oxide during lumbar punctures for pediatric leukemia and lymphoma patients. Paper presented at the APHON 32nd Annual Conference, Albuquerque, NM.
43. Sanders RD, Weimann J, Maze M. Biological effects of nitrous oxide Anesthesiology.. 2006;109:707–722
45. McClothlin J, Crouch K, Mickelsen RL. Control of nitrous oxide in dental operatories [National Institute for Occupational Safety and Health Web site] September, 1994. Available at: http://www.cdc.gov/niosh/docs/94-129/pdfs/94-129.pdf
. Accessed on: January 11, 2010.
46. Phan H, Nahata MC. Clinical uses of dexmedetomidine in pediatric patients Paediatr Drugs. 2008;10:46–69
47. Mason KP, Zurakowski D, Zgleszewski SE, et al. High dose dexmedetomidine as the sole sedative for pediatric MRI Paediatr Anaesth.. 2008;18:403–411
48. Koroglu A, Teksan H, Sagir O, et al. A comparision of the sedative, hemodynamic, and respiratory effects of dexmedetomidine and propofol in children undergoing magnetic resonance imaging Anesth Analg.. 2006;103:63–67
49. Berkenbosch JW, Wankum PC, Tobias JD. Prospective evaluation of dexmedetomidine for noninvasive procedural sedation in children Pediatr Crit Care Med.. 2005;6:435–439
50. Mason KP, Zgleszewski SE, Dearden JL, et al. Dexmedetomidine for pediatric sedation for computed tomography imaging studies Anesth Analg.. 2006;103:57–62
51. Gottschling S, Meyer S, Krenn T, et al. Propofol versus midazolam/ketamine for procedural sedation in pediatric oncology J Pediatr Hematol Oncol.. 2005;27:471–476
52. Hertzog J, Dalton H, Anderson B, et al. Prospective evaluation of propofol anesthesia in the pediatric intensive care unit for elective oncology procedures in ambulatory and hospitalized children Pediatrics.. 2000;106:742–747
53. Cechvala M, Christenson D, Eickhoff J, et al. Sedative preference of families for lumbar punctures in children with acute leukemia: propofol alone or propofol and fentanyl J Pediatr Hematol Oncol.. 2008;30:142–147
54. Hollman G, Schultz M, Eickhoff J, et al. Propofol-fentanyl versus propofol alone for lumbar puncture sedation in children with acute hematologic malignancies: propofol dosing and adverse events Pediatr Crit Care Med.. 2008;9:616–622
55. Jayabose S, Levendoglu-Tugal O, Giamelli J, et al. Intravenous anesthesia with propofol for painful procedures in children with cancer J Pediatr Hematol Oncol.. 2001;23:290–293
56. Keidan I, Berkenstadt H, Sisi A, et al. Propofol/remifentanil versus propofol alone for bone marrow aspiration in pediatric haemato-oncological patients Paediatr Anaesth.. 2001;11:297–301
57. Meneses C, de Freitas J, Castro C, et al. Safety of general anesthesia for lumbar puncture and bone marrow aspirate/biopsy in pediatric oncology patients J Pediatr Hematol Oncol.. 2009;31:465–470
58. Von Heijne M, Bredlov B, Soderhall S, et al. Propofol or propofol-alfentanil anesthesia for painful procedures in the pediatric oncology ward Paediatr Anaesth.. 2004;14:670–675