PEDIATRICS Vol. 108 No. 3 September 2001, pp. 824

Oranges and Apples: Sedation and Analgesia

To the Editor.

The vitriolic comments by Drs Freeman and Vining regarding various sedation/analgesia guidelines and Dr Coté's critical incident analysis of sedation-related adverse events underscore the need for the utilization of evidence in the evaluation of the safety of such practices.^1,2 Drs Freeman and Vining contend that sedation alone for a nonpainful procedure such as an electroencephalogram (EEG) is inherently safe. They therefore suggest that the use of chloral hydrate alone for an EEG does not warrant any monitoring or attendance by qualified medical personnel as mandated by the Joint Commission on Accreditation of Healthcare Organizations and recommended by the American Academy of Pediatrics. Furthermore, they contend that such mandates are unnecessary and fiscally onerous. The evidence does not support their contention. We agree that the majority of children who receive sedation, analgesia, or both for a diagnostic or therapeutic procedure experience good outcomes with no long-term sequelae. However, the fortunately low incidence of adverse events should not lead to the conclusion that such guidelines are unnecessary. In fact, contrary to the conclusion of Drs Freeman and Vining, the literature is replete with reports of sedation-related adverse events.^2-8 We would direct Drs Freeman and Vining to several large, well-conducted, prospective studies that have not only addressed the incidence of adverse events with chloral hydrate sedation but have also provided a denominator.^3-8 These studies are not anecdotal, have appropriate statistical analysis, and include patients who had adverse events after the administration of chloral hydrate alone, without other sedative or analgesic agents. Indeed, it is reports such as these that have led to the development of monitoring guidelines and personnel mandates to promote the safety of sedated children.

Although chloral hydrate in therapeutic doses is purported not to cause significant respiratory depression, it may still cause respiratory compromise by relaxing the muscles that support the tongue and upper airway including the geniohyoid and genioglossus muscles.⁹ In fact, it is this very property of chloral hydrate that is largely responsible for most of the serious adverse events including upper airway obstruction, hypoxia, and even death. Data from several studies have confirmed this risk. We have previously reported a 5.3% incidence of significant oxygen desaturation (90% of baseline) in 854 children who received chloral hydrate alone (mean dose: 65 mg/kg) for nonpainful procedures.³ Several of these children required a variety of interventions including supplemental oxygen, repositioning of the airway, stimulation, and bag and mask ventilation. Other investigators have reported a similar incidence of hypoxia. Pereira et al⁸ reported a 3.6% incidence of hypoxia in 110 children sedated with recommended doses of chloral hydrate to facilitate computerized axial tomography. These children also required interventions including extension and repositioning of the neck, supplemental oxygen administration, and/or suctioning of the airway. Another study of 295 children who received chloral hydrate for 326 computed tomography scans reported a 1.2% incidence of respiratory symptoms including wheezing in 1 child that resolved without intervention, aspiration of secretions in another that required suctioning, and 2 incidents of airway obstruction by the tongue that required endotracheal intubation.⁶ In a subsequent study evaluating the use of chloral hydrate for 300 magnetic resonance imaging scans, the same investigators reported a 4% incidence of hypoxia that required interventions in the majority of cases.⁷ Although none of the children in these studies experienced any permanent sequelae, it is likely that such sequelae were averted by vigilant monitoring that permitted early detection of hypoxia and appropriate intervention.

All of the aforementioned studies highlight the risks associated with the use of chloral hydrate and provide denominators. The critical incident analysis of Coté et al does not provide a denominator. Their report is nonetheless an important addition to the sedation literature because it provides additional insight into why sedation-related adverse events occur and identifies human error as a significant contributor to sedation-related disasters. The above data, as well as the aforementioned guidelines that were prompted by evidence drawn from such data, should clearly indicate to every medical practitioner (whether anesthesiologist, pediatrician, dentist, or neurologist) to monitor all children who receive chloral hydrate with a nurse or physician in attendance. There are no inherently safe sedatives or techniques for sedation. The safety of sedated children is largely dependent on appropriate monitoring by knowledgeable and skilled practitioners who are trained to respond with appropriate interventions. Widespread acceptance and implementation of nationally recommended and mandated sedation/analgesia guidelines will result in enhanced safety of sedated children. If it is not fiscally feasible for certain institutions to provide the necessary resources that ensure safe care of sedated children, then, perhaps their patients and families are better served by undergoing their procedures elsewhere.

Shobha Malviya, MD
Alan R. Tait, PhD
Terri Voepel-Lewis, BSN, MSN
Department of Anesthesiology
University of Michigan Health System
Ann Arbor, MI 48109-0211

Lynne G. Maxwell, MD
Department of Anesthesiology and Critical Care Medicine
Johns Hopkins University School of Medicine
Baltimore, MD 21287

REFERENCES

1. Freeman JM, Vining EPG Oranges and apples: sedation and analgesia [letter]. Pediatrics. 2000; 106:1519 [Free Full Text]
2. Coté CJ, Notterman DA, Karl HW, Weinberg JA, McCloskey C Adverse sedation events in pediatrics: a critical incident analysis of contributing factors [see comments]. Pediatrics. 2000; 105:805-814 [Abstract/Free Full Text]
3. Malviya S, Voepel-Lewis T, Tait AR Adverse events and risk factors associated with the sedation of children by nonanesthesiologists [published erratum appears in Anesth Analg 1998 Feb;86(2):227]. Anesth Analg. 1997; 85:1207-1213 [Abstract]
4. Malviya S, Voepel-Lewis T, Eldevik OP, Rockwell DT, Wong JH, Tait AR Sedation and general anaesthesia in children undergoing MRI and CT: adverse events and outcomes [In process citation]. Br J Anaesth. 2000; 84:743-748 [Abstract/Free Full Text]
5. Malviya S, Voepel-Lewis T, Prochaska G, Tait AR. Prolonged recovery and delayed side effects of sedation for diagnostic imaging studies in children. Pediatrics. 2000;105(3). Available at: http://www.pediatrics.org/cgi/content/full/105/3/e42
6. Greenberg SN, Faerber EN, Aspinall CT High dose chloral hydrate sedation for children undergoing CT. J Comput Assist Tomogr. 1991; 15:467-469 [Medline]
7. Greenberg SN, Faerber En, Aspinall CT, Adams RC High-dose chloral hydrate sedation for children undergoing MR imaging: safety and efficacy in relation to age. AJR Am J Roentgenol. 1993; 161:639-641 [Abstract/Free Full Text]
8. Pereira JK, Burrows PE, Richards HM, Chuang SH, Babyn PS Comparison of sedation regimens for pediatric outpatient CT. Pediatr Radiol. 1993; 23:341-343 [CrossRef][Medline]
9. Hershenson M, Brouillette RT, Olsen E, Hunt CE The effect of chloral hydrate on genioglossus and diaphragmatic activity. Pediatr Res. 1984; 18:516-519 [Medline]

To the Editor.

Drs Freeman and Vining feel that our study is unable to separate apples from oranges, but they have missed the forest for the trees.¹ They wish to separate out sedation from analgesia. I certainly agree that those are 2 different processes with 2 very different goals. However, drugs administered for either sedation or analgesia can result in airway obstruction, apnea, hypoventilation, and hypoxemia which, if left unrecognized and if the patient is not rescued, have led to neurologic injury and death.² The authors state that we lack a numerator/denominator ratio; we agree and pointed that out in the discussion. Would they say that simply because there is only 1 plane crash per many millions of flights that it is okay to ignore it because it would cost too much to correct the problem? Our study should be viewed as a first step in trying to define areas where the "system" failed and a patient was injured. Nowhere in our document did we describe chloral hydrate as an analgesic; however, I would refer the authors to the follow-up paper that more extensively discusses the medications used for sedation.³ It should be noted that 20 patients in our cohort received chloral hydrate; 13 sustained death or permanent neurologic injury. In 7 of these 13, chloral hydrate was the only medication administered whereas in 6 it was combined with other medications. Four of the 7 cases where chloral hydrate was the only sedating medication received the drug in an overdose, 2 received it in an unknown amount, and the seventh case received a standard dose of 60 mg/kg. I would point out that this child was in an unmonitored situation, exactly what Drs Freeman and Vining think is acceptable.¹

Drs Freeman and Vining question the validity of three of our examples where chloral hydrate was associated with injury. The child who received the 6000 mg of chloral hydrate and died was 13 years old; we do not know why the child received such an excessive dose for a dental procedure or why he was unmonitored. Contrary to Freeman and Vining's suggestion, the child from Mexico received only chloral hydrate (60 mg/kg) for an echocardiogram; he had pulmonary artery hypertension with ventricular septal defect and was on Digoxin. This child also was not on any monitors and developed respiratory depression with bradyarrhythmia within 10 minutes of receiving the chloral hydrate and died. It is possible that airway obstruction resulted in hypoventilation with a resultant acute rise in pulmonary artery pressure and worsening of his preexisting right to left shunt. Had this child had pulse oximetry and the physicians appreciated the impact of hypoventilation caused by chloral hydrate and the underlying medical condition this event may have been prevented. The third child received an overdose because the mother gave 2 prescriptions of chloral hydrate; the prescriptions were given at home without medical supervision. Each of these were used as examples of where the system can fail. Anybody can make a mistake: a physician, a nurse, a pharmacist, or a parent, even with chloral hydrate. Any child can have an unanticipated sensitivity to any medication regardless of its safety profile. When such errors or events occur, if the patient is not monitored, as Drs Freeman and Vining suggest, a fatal outcome may result. At this point in time, we have no way of knowing if the recommendations of the American Academy of Pediatrics regarding monitoring have resulted in improved safety but a lesson can be learned from my specialty. The letter of Drs Freeman and Vining is very reminiscent of the early letters in the anesthesiology literature that were critical of recovery room and operating room monitoring requirements. Years later it is very clear that the establishment of uniform specialty specific guidelines for monitoring and recovery of anesthetized patients has reduced anesthetic-associated mortality from 1:10 000 to approximately 1:400 000 anesthetics.^4-7 Our goal with the critical incident study of sedated children was to begin this same process of closely examining the safety issues related to sedating children, to draw people's attention to the need for uniformity of approach and monitoring, to stir the pot of discussion and, hopefully, improve the safety net for children.

The new Joint Commission on Accreditation of Healthcare Organization's Recommendations, which went into effect January 1, 2001, very succinctly point out the need to adequately observe/monitor patients and also for the individuals providing sedation to have the skills to rescue the patient from the next level of intended sedation.⁸ I agree that we need better data regarding numerators and denominators regarding risks from sedation. I would speculate that the risk is probably somewhere in the vicinity of 1:10 000 to 1:100 000 cases; it is the rarity of such events that makes it so difficult to study and makes some individuals critical of the need to think about it at all. However even with low risk, eg, 1:200 000, I suspect that Drs Freeman and Vining would feel very badly if their case happened to be that one child who died because someone was trying to save money by not monitoring the patient. The real systems issue is to get the health care industry (ie, the insurance industry) to recognize the need for this kind of vigilance so that hospitals and physicians are adequately reimbursed. Drs Freeman and Vining suggest that it is fiscally unsound to subsidize a nurse to monitor each child; I would say it is morally irresponsible to not monitor such children and to send them off to a facility that places their patients at risk. It is not our studies that prevent children from receiving care rather, it is the inability to be creative and proactive.

I am glad that we have stirred the pot of controversy and discussion and I look forward to Drs Freeman and Vining designing and conducting prospective, well-controlled studies that will give us the answers that they seek. The intention of our papers and for all sedation guidelines is to make things safe for children.

Charles J. Coté, MD
Department of Pediatric Anesthesiology
Children's Memorial Hospital
Department of Anesthesiology and Pediatrics
Northwestern University Medical School
Chicago, IL 60614

REFERENCES

1. Freeman JM, Vining EPG Oranges and apples: sedation and analgesia [letter]. Pediatrics. 2000; 106:1519
2. Coté CJ, Notterman DA, Karl HW, Weinberg JA, McCloskey C Adverse sedation events in pediatrics: a critical incident analysis of contributing factors [see comments]. Pediatrics. 2000; 105:805-814
3. Coté CJ, Karl HW, Notterman DA, Weinberg JA, McCloskey C Adverse sedation events in pediatrics: analysis of medications used for sedation. Pediatrics. 2000; 106:633-644 [Abstract/Free Full Text]
4. Eichhorn JH Effect of monitoring standards on anesthesia outcome. Int Anesthesiol Clin. 1993; 31:181-196 [Medline]
5. Eichhorn JH Pulse oximetry as a standard of practice in anesthesia. Anesthesiology. 1993; 78:423-426 [Medline]
6. Cullen DJ, Eichhorn JH, Cooper JB, Maier WR, Philip JH, Holzman RS, Gessner JS Postanesthesia care unit standards for anesthesiologists. J Post Anesth Nurs. 1989; 4:141-146 [Medline]
7. Eichhorn JH Prevention of intraoperative anesthesia accidents and related severe injury through safety monitoring. Anesthesiology. 1989; 70:572-577 [CrossRef][Medline]
8. Joint Commission on Accreditation of Healthcare Organizations. Comprehensive Accreditation Manual for Hospitals. Oakbrook Terrace, IL: Joint Commission on Accreditation of Healthcare Organizations; 2000

In Reply.

We appreciate the opportunity to respond to the letters of Drs Coté and Malviya et al and to have, as Coté states, "stirred the pot" regarding the confusion over sedation, analgesia, and the need for medical supervision for each.

Our letter was written in response to Cote's article¹ of April 2000 and preceded his article entitled "Adverse Sedation Events in Pediatrics: Analysis of Medications Used for Sedation."² In that second article Coté explains that of the 7 cases in his series who received chloral hydrate alone, 4 received an overdose, 2 received an unknown dose, and 1 (with pulmonary hypertension) received a standard dose. As Coté emphasizes, "anyone can make a mistake ... and any child can have an unanticipated sensitivity to medication, regardless of its safety profile." We agree, but we do not believe that even highly trained personnel monitoring an EEG can protect the child from the mother who gave 2 prescriptions of chloral hydrate at home, or from the mistakes of the health care professionals Coté cites.

We regret that our letter was misinterpreted by Malviya and colleagues as "vitriolic." She and her colleagues cite evidence that untoward events can have a denominator; a 5.3% incidence of significant oxygen desaturation in one paper, 3.6% in another, 1.2% in a third, and 4% in a fourth. The latter 2 studies used high-dose chloral hydrate for computed tomography scans and magnetic resonance imaging. Malviya concludes by stating, "There are no inherently safe sedatives or techniques for sedation. The safety of sedated children is dependent on appropriate monitoring by knowledgeable and skilled practioners ... appropriately trained ..." She then addresses the fiscal problems of this approach.

We did not suggest that "chloral hydrate ... does not warrant any monitoring or attendance by qualified medical personnel." We would agree that every child receiving chloral hydrate for an EEG should be monitored, but suggest using an oximeternot necessarily using a "licensed independent practioner ... qualified to rescue patients from deep sedation," as has recently been mandated by the Joint Commission on Accreditation of Healthcare Organizations.³ Couldn't the EEG technician respond to the monitor's alarm that might go off once in every 25 to 100 studies? Couldn't the magnetic resonance imaging technician do the same?

We would indeed feel badly if our patient were one of the 1:200 000 who died, but we think that the true issue may be captured in Coté's next sentence, which speaks to the need for the hospitals and physicians to be adequately reimbursed. In response to our statement that it is fiscally unsound to subsidize a nurse to monitor each child, Coté responds that it is, "morally irresponsible not to monitor each child." We agree with Lamm⁴ when he states, "You cannot build an ethical code for a publicly funded system (whether insurance or public funds) around the assumptions that cost is never a consideration ... cost is always a consideration." We must save the unwarranted costs from our health system to spend on our other social needs.

John M. Freeman, MD
Johns Hopkins University
Pediatric Epilepsy Center
Baltimore, MD 21287-7247

REFERENCES

1. Coté CJ, Karl HW, Notterman DA, Weinberg JA, McCloskey C Adverse sedation events in pediatrics: a critical incident analysis of contributing factors. Pediatrics. 2000; 105:805-814
2. Coté CJ, Karl HW, Notterman DA, Weinberg JA, McCloskey C Adverse sedation events in pediatrics: analysis of medications used for sedation. Pediatrics. 2000; 106:633-644
3. Joint Commission Perspectives. 2000;July/August, 11-12
4. Lamm D. Redrawing the ethics map. Hastings Cent Rep. March/April 1999