PEDIATRICS Vol. 106 No. 4 October 2000, pp. 742-747

Prospective Evaluation of Propofol Anesthesia in the Pediatric Intensive Care Unit for Elective Oncology Procedures in Ambulatory and Hospitalized Children

James H. Hertzog, MD^*, Heidi J. Dalton, MD^*, Barry D. Anderson, MD, PhD, Aziza T. Shad, MD, Joseph E. Gootenberg, MD, and Gabriel J. Hauser, MD^*

From the Department of Pediatrics, Divisions of ^* Pediatric Critical Care and Pulmonary Medicine and  Pediatric Hematology-Oncology, Georgetown University Medical Center, Washington, DC.

	ABSTRACT

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Objectives.  To evaluate our experience with propofol anesthesia delivered by pediatric intensivists in the pediatric intensive care unit (PICU) to facilitate elective oncology procedures in children performed by pediatric oncologists.

Methods.  Elective oncology procedures performed with propofol anesthesia in our multidisciplinary, university-affiliated PICU were prospectively evaluated over a 7-month period. Ambulatory and hospitalized children were prescheduled for their procedure, underwent a medical evaluation, and met fasting requirements before the start of anesthesia. Continuous cardiorespiratory and neurologic monitoring was performed by a pediatric intensivist and a PICU nurse, while the procedure was performed by a pediatric oncologist. Propofol was delivered in intermittent boluses to achieve the desired level of anesthesia. Information studied included patient demographics, procedures performed, induction and total doses of propofol used, the duration of the different phases of the patient's PICU stay, the occurrence of side effects, the need for therapeutic interventions, and the incidence of recall of the procedure.

Results.  Fifty procedures in 28 children (mean age: 7.5 ± 4.3 years) were evaluated. Sixty-one percent of patients had established diagnoses. Fifty-four percent of procedures were lumbar puncture with intrathecal chemotherapy administration and 26% of procedures were bone marrow aspirations with biopsy. Induction propofol doses were 2.0 ± .8 mg/kg for ambulatory and hospitalized patients, while total propofol doses were 6.6 ± 2.3 mg/kg and 7.9 ± 2.4 mg/kg for ambulatory and hospitalized patients, respectively. Induction time was 1.5 ± .7 minutes, recovery time was 23.4 ± 11.5 minutes, and total PICU time was 88.8 ± 27.7 minutes. Transient decreases in systolic blood pressure less than the fifth percentile for age occurred in 64% of procedures, with a mean decrease of 25% ± 10%. Intravenous fluids were administered in 31% of these cases. Hypotension was more common in ambulatory patients but was not predicted by propofol dose, anesthesia time, or age. Partial airway obstruction was noted in 12% of procedures while apnea requiring bag-valve-mask ventilation occurred in 2% of procedures. Neither was associated with age, propofol dose, or the duration of anesthesia. All procedures were successfully completed and there were no incidences of recall of the procedure.

Conclusions.  Propofol anesthesia is effective in achieving patient comfort and amnesia, while optimizing conditions for elective oncology procedures in children. Although transient hypotension and respiratory depression may occur, propofol anesthesia seems to be safe to use for these procedures in the PICU setting. Recovery from anesthesia was rapid and total stay was brief. Under the proper conditions, propofol anesthesia delivered by pediatric intensivists in the PICU is a reasonable option available to facilitate invasive oncology procedures in children.  Key words:  propofol, anesthesia, pediatrics, pediatric oncology, procedures, pediatric intensive care.

Bone marrow aspiration, bone marrow biopsy, and lumbar puncture with or without intrathecal chemotherapy administration are procedures that are necessary for the diagnosis and treatment of cancer. Although these procedures are typically short in duration, they cause pain and anxiety and must be repeated frequently. Children with cancer often find that such procedures are the most traumatic aspects of their care.¹ When untreated, the stress and discomfort associated with these procedures may produce a distress response by the child. This response may increase the duration of the procedure, may necessitate the use of physical restraint and increase the potential for injury to the child and to staff, and may become a significant source of stress for the staff and the child's parents.²

In response to these concerns, the American Academy of Pediatrics published recommendations on the management of pain and anxiety related to procedures in children with cancer in 1990.³ Subsequently, there have been increased efforts to manage the pain and stress of oncology-related procedures with psychological as well as pharmacological interventions.^1,2,4-14 Several pharmacologic agents have been used with varying success and occurrence of side effects. Attributable to the brief nature of these procedures, the ideal pharmacologic agent would have a rapid-onset of action, titratable level of effect, and short duration of activity once medication administration was discontinued. In addition, because these procedures are often performed in ambulatory patients, a rapid recovery from anesthesia so that patients could be allowed to go home soon after the completion of their procedure would be ideal. Furthermore, because these patients are receiving chemotherapeutic agents, an anesthetic that did not cause nausea and had antiemetic effects would be of benefit.

Propofol is an intravenously administered anesthetic with a rapid-onset of action, titratable level of effect, and short duration of activity once it is discontinued. Furthermore, propofol has antiemetic effects and patients tend to experience a clear headed emergence from propofol anesthesia.¹⁵ Propofol is being used more frequently outside of the operating room to facilitate a variety of procedures in children, including oncologic procedures,^13,14 but reports on its use in this situation have been few and retrospective in nature. We, therefore, performed a prospective analysis of our practice of administering propofol anesthesia in our pediatric intensive care unit (PICU) to children undergoing oncologic procedures to better understand the uses and limitations of this agent in this setting.

	METHODS

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A prospective observational evaluation of patients receiving propofol anesthesia to facilitate nonemergent oncologic procedures was performed in the PICU of Georgetown University Medical Center over a 7-month period. At our institution, propofol anesthesia delivered in the PICU is the standard of care for children undergoing elective oncology procedures. Informed consent for propofol anesthesia and the oncologic procedure was obtained from the parents of each patient. Data collected included the patient's age, weight, diagnosis, and origin (ambulatory vs hospitalized); procedure performed; propofol doses administered; occurrence of pain with propofol infusion; type of venous access; vital signs; the use of therapeutic interventions; the duration of the different phases of anesthesia and the procedure; the success of the procedure; and the occurrence of recall of the procedure. All data were collected at the convenience of a single investigator who did not participate in the delivery of anesthesia or the performance of the procedure.

Induction time was defined as the time from administration of the first dose of propofol to when the patient was unresponsive to verbal or tactile stimuli. Recovery time was defined as the time from administration of the last dose of propofol to when the patient had spontaneous eye opening or appropriate verbal responses or crying. Patients received verbal and tactile stimulation every 5 minutes after the completion of the procedure to decrease the possibility that the patient was asleep but no longer anesthetized. Hypotension was defined as a systolic blood pressure less than the fifth percentile of normal for age.¹⁶ Pain with injection of propofol was determined either by the child's verbal complaint or by withdrawal of the extremity in which the intravenous catheter was placed on initial delivery of propofol.

Our protocol for delivering propofol anesthesia in the PICU has been previously described¹⁴ and is approved by the chairs of the departments of pediatrics and anesthesiology. Ambulatory and hospitalized patients are electively scheduled for their anesthesia and procedure. All patients undergo a medical evaluation before their anesthesia, including a review of past and current medical problems, previous individual and family experiences with anesthesia, and the occurrence of allergic reactions; a physical examination of the cardiorespiratory and neurologic systems; and a review of laboratory studies. Patients are required to fast before their anesthesia as outlined by the American Academy of Pediatrics and the American Society of Anesthesiologists.^17,18 Milk and solid foods are withheld for at least 4 hours in children <6 months of age, 6 hours in children between 6 and 36 months of age, and 8 hours in older children. All children are allowed clear liquids up to 2 hours before the procedure if desired. Intravenous access is achieved either through an indwelling central venous catheter when available or through a catheter placed in a peripheral vein.

Cardiorespiratory monitoring, including continuous electrocardiography, respiratory rate, and pulse oximetry measurements and intermittent (every 2 minutes) noninvasive blood pressure measurements, is instituted before the start of anesthesia and continued until recovery. A pediatric intensivist, or a fellow in pediatric critical care medicine under the direct supervision of a pediatric intensivist, and a PICU nurse provide continuous monitoring of the patient's cardiorespiratory status and level of anesthesia. The oncologic procedure is performed by the pediatric oncologist without direct assistance by the PICU physician or nurse. Written documentation of the course of the anesthesia is recorded on a standardized form. All equipment and medications needed for cardiorespiratory support are made available at the patient's bedside. Monitoring is discontinued and the child is discharged to home or back to their inpatient unit when they met standardized discharge criteria,¹⁷ which includes the normalization of vital signs and airway control, full wakefulness, the ability to tolerate enteral intake, and the ability to talk and sit without assistance if age-appropriate.

Propofol is administered at the discretion of the pediatric intensivist or the fellow in pediatric critical care medicine under the direction of the pediatric intensivist. Propofol is given in intermittent boluses, with the objective of keeping the patient unconscious and comfortable with minimal to no movement, while assuring patient safety and minimum side effects during the course of the procedure. All patients receive supplemental oxygen via blow-by from the bag-valve-mask resuscitator throughout their anesthesia. In those patients with peripheral intravenous catheters in place, 10 mg of lidocaine is mixed with the initial 90 mg of propofol in an attempt to decrease the local pain that may occur when propofol is injected into a small vein. Because propofol has no analgesic effects, eutectic mixture of local anesthetics cream is placed before the procedure when possible and 1% lidocaine infiltration at the procedure site is performed by the pediatric oncologist after the patient is anesthetized. Therapeutic interventions are initiated as needed as directed by the pediatric intensivist.

Results are expressed as mean ± standard deviation (SD). Comparison of means between groups was analyzed with 2-tailed Student's t test for independent samples or the Mann-Whitney U test. The relationship between dependent and independent variables was evaluated with multiple regression analysis. A P value .05 was considered statistically significant. All statistical tests were performed with the SPSS for MS Windows Release 6.1 computer program (SPSS, Inc, Chicago, IL).

	RESULTS

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During a 7-month period, 50 propofol anesthesias to facilitate oncologic procedures in 28 patients were prospectively evaluated. Patient demographics are presented in Table 1. Fifty percent of the patients underwent only 1 propofol anesthetic in this series, with another 29% and 18% of the patients having 2 or 3 propofol anesthetics, respectively. One patient had a total of 5 propofol anesthetics in this series. The oncologic procedures performed are presented in Table 2. Lumbar puncture with intrathecal chemotherapy administration was the most commonly performed procedure in ambulatory patients, while hospitalized patients underwent bone marrow aspiration and biopsy most frequently.

Table 3 shows induction and total propofol doses used for ambulatory and hospitalized patients. No difference is noted between these 2 groups of patients in the doses of propofol used (P > .05). The durations of the various stages of the patient's stay in the PICU are shown in Table 4. No difference in the length of any of the stages between ambulatory and hospitalized patients was demonstrated (P > .05).

The occurrence of side effects and the utilization of therapeutic interventions are presented in Table 5. Decreases in systolic blood pressure to less than the fifth percentile for age were common, occurring in 64% of procedures and in 68% of patients. The mean decrease in systolic blood pressure was 25% ± 10%. No hypotension was present before the initiation of anesthesia. Periods of hypotension were commonly transient and would resolve without therapy. In 31% of those cases where hypotension was seen, intravenous fluid was administered. No vasoactive agents were required. Periods of hypotension were never associated with an alteration in the quality of peripheral pulses or perfusion. Induction and total doses of propofol and total anesthesia time were not predictive of the development of hypotension (P > .05). There was, however, a trend for older patients to develop hypotension (P = .08). Additionally, episodes of hypotension were more common in ambulatory patients, occurring in 72% of procedures versus 36% of the procedures in hospitalized patients (P = .03). There was, however, no difference in ages between ambulatory and hospitalized patients. Of the 10 cases where intravenous fluid was administered, 9 cases involved ambulatory patients.

A decrease in oxygen saturation to <92% despite supplemental oxygen was seen in 2 patients. In 1 patient, the oxygen saturation decreased to 91% after the induction dose of propofol and subsequently rose with no intervention. The second patient developed apnea after induction with propofol and required repositioning of the airway and bag-valve-mask ventilation for <30 seconds before regaining an adequate respiratory drive. Partial airway obstruction was noted in 6 patients. One of these patients was the child who developed apnea as described above. The other 5 children did not experience a decrease in their oxygen saturation, and their clinical signs of partial airway obstruction resolved with a head tilt/neck extension maneuver. Placement of an oral or nasopharyngeal airway was not required. No relationship between the development of decreased oxygen saturation, partial airway obstruction, or apnea and the patient's age, the induction or total dose of propofol, or the duration of anesthesia was evident (P > .05).

All procedures were successfully completed. For 33 procedures in 18 patients who were old enough to reply, there was no recall of the procedure.

	DISCUSSION

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Invasive procedures that must be repeated over a patient's course of therapy, such as bone marrow aspiration and lumbar puncture, are a necessary part of the management of childhood cancer. These procedures are painful and commonly produce anxiety and distress in children. An important priority for the health care providers of children with cancer is to relieve this distress response and the adverse effects associated with it. When the distress associated with procedures is successfully relieved, the child will be comfortable and able to tolerate procedures and should not develop anticipatory distress about future procedures.³

Many pharmacologic agents have been used to help relieve the distress response associated with oncologic procedures in children. However, no one agent has been found that provides a titratable level of sedation and which is devoid of side effects. Midazolam, a short-acting benzodiazepine, is often used for sedation during oncologic procedures. In a study of the use of midazolam by oncologists to facilitate 70 procedures in 24 ambulatory children, full or partial amnesia was reported in 90% of the procedures. However, physical restraint was necessary in 55% of procedures and transient hypoxemia occurred in 13% of procedures.⁴ In another study of 25 children undergoing 77 procedures that compared midazolam to fentanyl, a short-acting synthetic narcotic, total amnesia was achieved in 91% of procedures with midazolam versus 35% of procedures with fentanyl. There was no statistical improvement in preprocedural anxiety, adverse behavioral symptoms, or anticipated pain, however, with either regimen.⁵ Oral ketamine was used in 35 children before oncologic procedures and was found to produce low levels of procedure-related distress in three quarters of the patients. However, an adequate level of sedation was not achieved in most children until 45 minutes after medication, and 2 to 4 hours were required before patients met discharge criteria.⁶ Methohexital, a short-acting barbiturate, was used to facilitate procedures in 33 outpatients undergoing 132 procedures. In 17.4% of procedures, the patient's blood pressure or heart rate was recorded outside of the normal range for age. There were minor complications requiring no intervention in 6.1% of patients and complications requiring intervention in 5.3% of patients.⁷ In a study comparing oral transmucosal fentanyl to placebo, ratings of pain were significantly reduced with oral transmucosal fentanyl, but 74% of the patients were fully awake for the procedure and one third of the patients experienced nausea and vomiting.⁸ The combination of intravenous ketamine and midazolam was compared with merperidine and midazolam in a crossover trial in 18 children. Ketamine and midazolam resulted in less behavioral distress, more rapid achievement of sedation, and more rapid recovery from sedation with fewer side effects than merperidine and midazolam. Failure to adequately sedate the patient occurred in 11% of the ketamine-midazolam patients, whereas hypoxia and emergence reactions were noted during 17% and 33% of the cases, respectively.¹⁰ A retrospective review of the use of propofol, ketamine, or etomidate by pediatric anesthesiologists outside of the operating room demonstrated an exceedingly rare occurrence of emesis and postanesthesia agitation when propofol was used. However, a 16% occurrence of hypoxia secondary to hypoventilation or apnea was noted.¹³

Although multiple pharmacologic agents are available for sedating or anesthetizing children during oncologic procedures, each agent has advantages and disadvantages. Propofol has several characteristics that make it ideal for use in brief procedures. Induction and recovery times are generally rapid, and the depth of anesthesia is readily titratable. In addition, patients tend to have a smooth emergence from anesthesia and are not nauseated secondary to the antiemetic effects of propofol, making it more likely that they will meet discharge criteria more rapidly than with other agents.¹⁵ The practice in our institution has been to use propofol to facilitate a variety of procedures in the PICU setting, which we have retrospectively reviewed.¹⁴ We found that propofol anesthesia was associated with short induction times (3.4 ± 2.4 minutes), recovery times (30.7 ± 20.4 minutes), and total PICU length of stay (146.8 ± 107.9 minutes) in ambulatory patients. Important side effects were noted. Hypotension occurred in 50% of cases. Periods of hypotension were generally brief and were not associated with a change in the patient's peripheral pulses or capillary refill. Respiratory depression requiring brief periods of bag-valve-mask ventilation but not requiring tracheal intubation occurred in 6% of cases.

In our retrospective review, oncologic procedures accounted for 61% of all procedures.¹⁴ Because oncologic procedures represent the majority of elective procedures that we perform with propofol anesthesia in our PICU, and because no prospective analysis of this practice has been performed, we elected to prospectively evaluate this practice to better understand its benefits and drawbacks. Propofol anesthesia for elective oncologic procedures is associated with short induction and recovery times as well as a short total length of stay in the PICU. These times are much shorter than those found in our retrospective review, as would be expected from the improved documentation of timing, the active attempts to waken patients, and the greater experience of the personnel in delivering propofol anesthesia at the time of the prospective study. The rapidity of the completion of the total procedure is important, because the added cost of using propofol anesthesia in the PICU setting would ideally be offset by the shorter procedure and observation times required with propofol versus other agents that may not produce as ideal operating conditions or that may have a prolonged recovery phase. We also believe that propofol anesthesia provides a setting in which procedures are more easily completed with less patient distress and subsequent procedure related anticipatory anxiety than is associated with other types of sedation. Our patients experience a smooth emergence from propofol anesthesia with no recall of the procedure and no nausea, even when intrathecal chemotherapy has been administered. We have found that once a patient has been given propofol to facilitate a procedure, they and their parents wish to continue to receive this agent rather than another sedative medication.

As was expected from the pharmacologic effects of propofol that have been previously reported and our prior experience, important side effects occurred. Hypotension occurred commonly. These periods of hypotension were brief and not associated with other signs or symptoms of impaired cardiac output. One possible contribution to this incidence is that standards for blood pressure are taken in children who are awake and, if old enough, seated rather than supine and anesthetized.¹⁶ It would be expected that blood pressure would be decreased to a certain extent by the anxiolytic effect of the anesthetic. Unfortunately, blood pressure standards for anesthetized children are not available. It is interesting that hypotension occurred more frequently in older children and in outpatients. Our experience has been that older children tend to abstain from clear liquid ingestion for longer periods of time before their anesthesia than do younger children. In addition, patients who are hospitalized are more likely to receive intravenous fluids during the period when they are fasting. It is possible, therefore, that older children and outpatients experience hypotension more frequently, because they have a greater fluid deficit at the start of anesthesia than do younger children and inpatients. Because propofol causes vasodilation, relatively small differences in volume status may result in greater degrees of hypotension in these patients. The more common use of intravenous fluid administration in outpatients in response to hypotension is consistent with this possibility. It may be reasonable to provide intravenous fluid replacement of the calculated deficit before and during propofol anesthesia in an effort to decrease the incidence of hypotension.

Respiratory events, including partial airway obstruction, hypoxemia, and apnea occurred infrequently and at a rate demonstrated in our retrospective review.¹⁴ Partial airway obstruction was the most common respiratory problem encountered and was generally relieved with a head tilt/neck extension maneuver. Apnea occurred in an 11-year-old girl who was undergoing a bone marrow aspiration for evaluation of cytopenia. This was the first invasive procedure that the patient had experienced, and she was quite anxious before the start of anesthesia. Furthermore, she experienced pain with the initial infusion of propofol through her peripheral intravenous catheter, which further heightened her anxiety. Although her induction dose was not significantly different from the other patients, it is likely that it was infused more rapidly than usual. This may have contributed to her development of apnea. After a brief period of bag-valve-mask ventilation, the patient regained an adequate respiratory drive and the procedure was completed without further complication. Further investigations on the role of infusion rate on the development of side effects would be of interest.

Propofol is a potent intravenous anesthetic agent and, as has been described, its administration can be associated with the development of significant side effects. Therefore, it is essential that propofol be administered by practitioners who understand its use and are capable of treating its side effects, including apnea and hypotension. Propofol should only be administered in an environment where appropriate monitoring, resuscitation equipment, and personnel are available. Although our preference is to use propofol to facilitate oncologic procedures in children, it is unknown whether the benefits and risks of this approach outweigh the benefits and risks associated with other pharmacologic agents that are currently used by many oncologists to produce conscious sedation. A prospective comparative evaluation of these different approaches may provide further insight into this issue.

	CONCLUSION

Top Abstract Methods Results Discussion Conclusion References

We prospectively evaluated our experience with propofol anesthesia to facilitate elective oncology procedures in the PICU. Propofol anesthesia was effective in achieving patient comfort and amnesia, while optimizing the conditions for the procedure. Although transient hypotension was common and respiratory depression was infrequent, propofol anesthesia seems to be safe to use for these procedures in the PICU setting. Recovery from anesthesia was rapid and total stay was brief. Under the proper conditions, propofol anesthesia delivered by pediatric intensivists in the PICU is a reasonable option available to facilitate invasive procedures in pediatric oncology patients.

	FOOTNOTES

Received for publication Sep 30, 1999; accepted Jan 18, 2000.

This work was presented in part at the 11th Annual Pediatric Critical Care Colloquium; September 17, 1998; Chicago, IL.

Reprint requests to (J.H.H.) Department of Anesthesiology and Critical Care Medicine, AI duPont Hospital for Children, 1600 Rockland Rd, Wilmington, DE 19803. E-mail: jhertzog{at}nemours.org

	ABBREVIATIONS

PICU, pediatric intensive care unit; SD, standard deviation.

	REFERENCES

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1. Jay SM, Elliott CH, Woody PD, Siegel S An investigation of cognitive-behavior therapy combined with oral valium for children undergoing painful medical procedures. Health Psychol 1991; 10:317-322 [CrossRef][Medline]
2. Powers SW, Blount RL, Bachanas PJ, Cotter MW, Swan SC Helping preschool leukemia patients and their parents cope during injections. J Pediatr Psychol 1993; 18:681-695 [Abstract/Free Full Text]
3. Zeltzer LK, Altman A, Cohen D, LeBaron S, Munuksela EL, Schechter NL Report of the subcommittee on the management of pain associated with procedures in children with cancer. Pediatrics 1990; 86:826-831 [Abstract/Free Full Text]
4. Sievers TD, Yee JD, Foley ME, Blanding PJ, Berde CB Midazolam for conscious sedation during pediatric oncology procedures: safety and recovery parameters. Pediatrics 1991; 88:1172-1179 [Abstract/Free Full Text]
5. Sandler ES, Weyman C, Conner K, Midazolam versus fentanyl as premedication for painful procedures in children with cancer. Pediatrics 1992; 89:631-634 [Medline]
6. Tobias JD, Phipps S, Smith B, Mulhern RK Oral ketamine premedication to alleviate the distress of invasive procedures in pediatric oncology patients. Pediatrics 1992; 90:537-541 [Abstract/Free Full Text]
7. Schwanda AE, Freyer DR, Sanfilippo DJ, Brief unconscious sedation for painful pediatric oncology procedures. Am J Pediatr Hematol Oncol 1993; 15:370-376 [Medline]
8. Schechter NL, Weisman SJ, Rosenblum M, Bernstein B, Conard PL The use of oral transmucosal fentanyl citrate for painful procedures in children. Pediatrics 1995; 95:335-339 [Abstract/Free Full Text]
9. Jay S, Elliott CH, Fitzgibbons I, Woody P, Siegel S A comparative study of cognitive behavior therapy versus general anesthesia for painful medical procedures in children. Pain 1995; 62:3-9 [CrossRef][Medline]
10. Marx CM, Stein J, Tyler MK, Nieder ML, Shurin SB, Blumer JL Ketamine-midazolam versus meperidine-midazolam for painful procedures in pediatric oncology patients. J Clin Oncol 1997; 15:94-102 [Abstract/Free Full Text]
11. Kazak AE, Penati B, Brophy P, Himelstein B Pharmacologic and psychologic interventions for procedural pain. Pediatrics 1998; 102:59-66 [Abstract/Free Full Text]
12. Slonim AD, Ognibene FP Sedation for pediatric procedures, using ketamine and midazolam, in a primarily adult intensive care unit: a retrospective evaluation. Crit Care Med 1998; 26:1900-1904 [Medline]
13. McDowall RH, Scher CS, Barst SM Total intravenous anesthesia for children undergoing brief diagnostic or therapeutic procedures. J Clin Anesth 1995; 7:273-280 [CrossRef][Medline]
14. Hertzog JH, Campbell JK, Dalton HJ, Hauser GJ. Propofol anesthesia for invasive procedures in ambulatory and hospitalized children: experience in the pediatric intensive care unit. Pediatrics. 1999;103(3). URL: http://www.pediatrics.org/cgi/content/full/103/3/e30
15. Watcha MF Intravenous anesthesia for pediatric patients. Curr Opin Anaesthesiol 1993; 6:515-522
16. Blumenthal S, Epps RP, Heavenrich R, Report of the task force on blood pressure control in children. Pediatrics 1977; 59:797-820
17. 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 [Abstract/Free Full Text]
18. American Society of Anesthesiologists, Task Force on Sedation and Analgesia by Non-Anesthesiologists Practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology 1996; 84:459-471 [CrossRef][Medline]