Charles J. Coté

Guidelines for Monitoring and Management of Pediatric Patients During and After Sedation for Diagnostic and Therapeutic Procedures: An Update

The safe sedation of children for procedures requires a systematic approach that includes the following: no administration of sedating medication without the safety net of medical supervision; careful presedation evaluation for underlying medical or surgical conditions that would place the child at increased risk from sedating medications; appropriate fasting for elective procedures and a balance between depth of sedation and risk for those who are unable to fast because of the urgent nature of the procedure; a focused airway examination for large tonsils or anatomic airway abnormalities that might increase the potential for airway obstruction; a clear understanding of the pharmacokinetic and pharmacodynamic effects of the medications used for sedation, as well as an appreciation for drug interactions; appropriate training and skills in airway management to allow rescue of the patient; age- and size-appropriate equipment for airway management and venous access; appropriate medications and reversal agents; sufficient numbers of people to carry out the procedure and monitor the patient; appropriate physiologic monitoring during and after the procedure; a properly equipped and staffed recovery area; recovery to presedation level of consciousness before discharge from medical supervision; and appropriate discharge instructions. This report was developed through a collaborative effort of the American Academy of Pediatrics and the American Academy of Pediatric Dentistry to offer pediatric providers updated information and guidance in delivering safe sedation to children.

Adverse sedation events in pediatrics: a critical incident analysis of contributing factors.

Objective. Factors that contribute to adverse sedation events in children undergoing procedures were examined using the technique of critical incident analysis. Methodology. We developed a database that consists of descriptions of adverse sedation events derived from the Food and Drug Administrations adverse drug event reporting system, from the US Pharmacopeia, and from a survey of pediatric specialists. One hundred eighteen reports were reviewed for factors that may have contributed to the adverse sedation event. The outcome, ranging in severity from death to no harm, was noted. Individual reports were first examined separately by 4 physicians trained in pediatric anesthesiology, pediatric critical care medicine, or pediatric emergency medicine. Only reports for which all 4 reviewers agreed on the contributing factors and outcome were included in the final analysis. Results. Of the 95 incidents with consensus agreement on the contributing factors, 51 resulted in death, 9 in permanent neurologic injury, 21 in prolonged hospitalization without injury, and in 14 there was no harm. Patients receiving sedation in nonhospital-based settings compared with hospital-based settings were older and healthier. The venue of sedation was not associated with the incidence of presenting respiratory events (eg, desaturation, apnea, laryngospasm, ∼80% in each venue) but more cardiac arrests occurred as the second (53.6% vs 14%) and third events (25% vs 7%) in nonhospital-based facilities. Inadequate resuscitation was rated as being a determinant of adverse outcome more frequently in nonhospital-based events (57.1% vs 2.3%). Death and permanent neurologic injury occurred more frequently in nonhospital-based facilities (92.8% vs 37.2%). Successful outcome (prolonged hospitalization without injury or no harm) was associated with the use of pulse oximetry compared with a lack of any documented monitoring that was associated with unsuccessful outcome (death or permanent neurologic injury). In addition, pulse oximetry monitoring of patients sedated in hospitals was uniformly associated with successful outcomes whereas in the nonhospital-based venue, 4 out of 5 suffered adverse outcomes. Adverse outcomes despite the benefit of an early warning regarding oxygenation likely reflect lack of skill in assessment and in the use of appropriate interventions, ie, a failure to rescue the patient. Conclusions. This study—a critical incident analysis—identifies several features associated with adverse sedation events and poor outcome. There were differences in outcomes for venue: adverse outcomes (permanent neurologic injury or death) occurred more frequently in a nonhospital-based facility, whereas successful outcomes (prolonged hospitalization or no harm) occurred more frequently in a hospital-based setting. Inadequate resuscitation was more often associated with a nonhospital-based setting. Inadequate and inconsistent physiologic monitoring (particularly failure to use or respond appropriately to pulse oximetry) was another major factor contributing to poor outcome in all venues. Other issues rated by the reviewers were: inadequate presedation medical evaluation, lack of an independent observer, medication errors, and inadequate recovery procedures. Uniform, specialty-independent guidelines for monitoring children during and after sedation are essential. Age and size-appropriate equipment and medications for resuscitation should be immediately available regardless of the location where the child is sedated. All health care providers who sedate children, regardless of practice venue, should have advanced airway assessment and management training and be skilled in the resuscitation of infants and children so that they can successfully rescue their patient should an adverse sedation event occur.

Adverse sedation events in pediatrics : Analysis of medications used for sedation

Objectives. To perform a systematic investigation of medications associated with adverse sedation events in pediatric patients using critical incident analysis of case reports. Methods. One hundred eighteen case reports from the adverse drug reporting system of the Food and Drug Administration, the US Pharmacopoeia, and the results of a survey of pediatric specialists were used. Outcome measures were death, permanent neurologic injury, prolonged hospitalization without injury, and no harm. The overall results of the critical incident analysis are reported elsewhere. The current investigation specifically examined the relationship between outcome and medications: individual and classes of drugs, routes of administration, drug combinations and interactions, medication errors and overdoses, patterns of drug use, practitioners, and venues of sedation. Results. Ninety-five incidents fulfilled study criteria and all 4 reviewers agreed on causation; 60 resulted in death or permanent neurologic injury. Review of adverse sedation events indicated that there was no relationship between outcome and drug class (opioids; benzodiazepines; barbiturates; sedatives; antihistamines; and local, intravenous, or inhalation anesthetics) or route of administration (oral, rectal, nasal, intramuscular, intravenous, local infiltration, and inhalation). Negative outcomes (death and permanent neurologic injury) were often associated with drug overdose (n = 28). Some drug overdoses were attributable to prescription/transcription errors, although none of 39 overdoses in 34 patients seemed to be a decimal point error. Negative outcomes were also associated with drug combinations and interactions. The use of 3 or more sedating medications compared with 1 or 2 medications was strongly associated with adverse outcomes (18/20 vs 7/70). Nitrous oxide in combination with any other class of sedating medication was frequently associated with adverse outcomes (9/10). Dental specialists had the greatest frequency of negative outcomes associated with the use of 3 or more sedating medications. Adverse events occurred despite drugs being administered within acceptable dosing limits. Negative outcomes were also associated with drugs administered by nonmedically trained personnel and drugs administered at home. Some injuries occurred on the way to a facility after administration of sedatives at home; some took place in automobiles or at home after discharge from medical supervision. Deaths and injuries after discharge from medical supervision were associated with the use of medications with long half-lives (chloral hydrate, pentobarbital, promazine, promethazine, and chlorpromazine). Conclusions. Adverse sedation events were frequently associated with drug overdoses and drug interactions, particularly when 3 or more drugs were used. Adverse outcome was associated with all routes of drug administration and all classes of medication, even those (such as chloral hydrate) thought to have minimal effect on respiration. Patients receiving medications with long plasma half-lives may benefit from a prolonged period of postsedation observation. Adverse events occurred when sedative medications were administered outside the safety net of medical supervision. Uniform monitoring and training standards should be instituted regardless of the subspecialty or venue of practice. Standards of care, scope of practice, resource management, and reimbursement for sedation should be based on the depth of sedation achieved (ie, the degree of vigilance and resuscitation skills required) rather than on the drug class, route of drug administration, practitioner, or venue.

A Single-blind Study of Pulse Oximetry in Children

Oxygen saturation determined by pulse oximetry was monitored in 152 pediatric surgical patients divided into two groups. In one group, the oximeter data and alarms were available (N = 76) to the anesthesia team, and, in the other group, these data were unavailable (N = 76). A trained observer recorded all intraoperative hypoxic episodes and informed the anesthesia team of all major events (i.e., oxygen saturation less than or equal to 85% for greater than or equal to 30 s) (PaO2 approximately 52 mmHg). Thirty-five major events occurred: 24 in the unavailable group, and 11 in the available group (P = 0.021). A greater number of major events occurred in children less than or equal to 2 yr of age (P = 0.013). Hypoxic events diagnosed by the oximeter, but not by the anesthesiologist, were more frequent in the unavailable group (13) than in the available group (5) (P = 0.0495). ASA Physical Status 3 and 4 patients were more likely to suffer a major event (P = 0.009 available, 0.006 unavailable). The pulse oximeter diagnosed hypoxemia before the signs and symptoms of hypoxemia were apparent (i.e., prior to observed cyanosis or bradycardia). Major hypoxic events were unrelated to duration of anesthesia. Major events were evenly distributed among induction, maintenance, and awakening from anesthesia; a greater number of hypoxic events occurred during induction in the unavailable group (P = 0.031). No morbidity was documented in any patient who suffered an hypoxic event.(ABSTRACT TRUNCATED AT 250 WORDS)

Sedation for the Pediatric Patient: A Review

Safe sedation of a pediatric patient requires a thorough knowledge of the pharmacokinetics and pharmacodynamics of the drugs used to sedate the patient and the skills necessary to deal effectively with potential adverse events as a result of the sedation. The Sedation Guidelines of the American Academy of Pediatrics are reviewed. Emphasis is placed on monitoring and appropriate selection of drugs.

Life-threatening Apnea in Infants Recovering from Anesthesia

To determine whether prematurely born infants with a history of idiopathic apneic episodes are more prone than other infants to life-threatening apnea during recovery from anesthesia, the authors prospectively studied 214 infants (173 full term, 41 premature) who received anesthesia. Fifteen premature infants had a preanesthetic history of idiopathic apnea. Six of these required mechanical ventilation because of idiopathic apneic episodes during emergence from anesthesia. Two were ventilated for other reasons, and seven recovered normally. Infants ventilated for apnea were younger (postnatal age 1.6 +/- 1.2 months, mean +/- SD; conceptual age 38.6 +/- 3.0 weeks) than those who recovered normally (postnatal age 5.6 +/- 2.7 months; conceptual age 55.1 +/- 11.3 weeks) (P less than 0.01). No other premature or full-term infant was ventilated because of postoperative apneic episodes. The authors conclude that anesthetics may unmask a defect in ventilatory control of prematurely born infants younger than 41-46 weeks conceptual age who have a preanesthetic history of idiopathic apnea.

twenty-four-hour Pharmacokinetics of Rectal Acetaminophen in Children : an Old Drug with New Recommendations

Background: Rectal acetaminophen is often administered during operation to provide supplemental analgesia or antipyresis in children. Recent studies examining current dose guidelines are limited by short sampling times. The authors extended the drug sampling period to more clearly define acetaminophen pharmacokinetics in children having surgery. Methods: Children (n = 28) were randomized to receive a single dose of 10, 20, or 30 mg/kg rectal acetaminophen after induction of anesthesia. Venous blood samples were taken every 30 min for 4 h, every 60 min for 4 h, and every 4 h for 16 h. Data were analyzed using a mixed‐effects modeling technique (using NONMEM software) to determine the volume of distribution and clearance normalized for bioavailability. Additional models accounted for suppository dissolution followed by acetaminophen absorption. Results: Age, weight, estimated blood loss, volume of intravenous fluid administered, and anesthesia time were similar in the three groups. Most patients did not achieve peak or sustained serum values in the 10–20 micro gram/ml serum concentration range associated with antipyresis. The volume of distribution was 385 ml/kg, and clearance normalized for bioavailability, F, was 5.46 ml [center dot] kg sup ‐1 [center dot] min sup ‐1. Pharmacokinetic models suggest that absorption of acetaminophen is a function of zero‐order dissolution of suppositories and first‐order absorption from the rectum. Suppository dose size also may affect absorption characteristics. Conclusions: The current recommended rectal acetaminophen dose of 10–15 mg/kg yields peak serum concentrations less than the antipyretic serum concentration of 10–20 micro gram/ml. Based on the observed kinetics, the authors recommend that the initial dose should be approximately 40 mg/kg.

Induction and maintenance characteristics of anesthesia with desflurane and nitrous oxide in infants and children.

To determine the induction and maintenance characteristics of desflurane in pediatric patients, the authors anesthetized 206 infants and children aged 1 month to 12 yr with nitrous oxide plus desflurane and/or halothane in oxygen. Patients were assigned to one of four groups: anesthesia was 1) induced and maintained with desflurane after premedication with an oral combination of meperidine, diazepam, and atropine; 2) induced and maintained with desflurane; 3) induced with halothane and maintained with desflurane; or 4) induced and maintained with halothane. An unblinded observer recorded time to loss of consciousness (lid reflex), time to intubation, and clinical characteristics of the induction and maintenance of anesthesia. Moderate-to-severe laryngospasm (49%) and moderate-to-severe coughing (58%) occurred frequently during induction of anesthesia with desflurane; the incidence of these was not altered by premedication. In contrast, laryngospasm and coughing were rare during induction of anesthesia with halothane. In unpremedicated patients, time to loss of lid reflex (mean +/- SD) was similar for desflurane (2.4 +/- 1.2 min) and halothane (2.1 +/- 0.8 min). During induction of anesthesia, before laryngoscopy and intubation, mean arterial pressure less than 80% of baseline was more common with halothane; heart rate and mean arterial pressure greater than 120% of baseline were more common with desflurane. Intraoperatively, heart rate greater than 120% of baseline was more common with desflurane; blood pressures were similar for the two anesthetics. The authors conclude that the high incidence of airway complications during induction of anesthesia with desflurane limits its utility for inhalation induction in pediatric patients. Anesthesia can be safely maintained with desflurane if induced with a different anesthetic.

A comparison of three doses of a commercially prepared oral midazolam syrup in children.

Midazolam is widely used as a preanesthetic medication for children. Prior studies have used extemporaneous formulations to disguise the bitter taste of IV midazolam and to improve patient acceptance, but with unknown bioavailability. In this prospective, randomized, double-blinded study we examined the efficacy, safety, and taste acceptability of three doses (0.25, 0.5, and 1.0 mg/kg, up to a maximum of 20 mg) of commercially prepared Versed® syrup (midazolam HCl) in children stratified by age (6 mo to <2 yr, 2 to <6 yr, and 6 to <16 yr). All children were ASA class I–III scheduled for elective surgery. Subjects were continuously observed and monitored with pulse oximetry. Ninety-five percent of patients accepted the syrup, and 97% demonstrated satisfactory sedation before induction. There was an apparent relationship between dose and onset of sedation and anxiolysis (P < 0.01). Eight-eight percent had satisfactory anxiety ratings at the time of attempted separation from parents, and 86% had satisfactory anxiety ratings at face mask application. The youngest age group recovered earlier than the two older age groups (P < 0.001). There was no relationship between midazolam dose and duration of postanesthesia care unit stay. Before induction, there were no episodes of desaturation, but there were two episodes of nausea and three episodes of emesis. At the time of induction, during anesthesia, and in the postanesthesia care unit, there were several adverse respiratory events. Oral midazolam syrup is effective for producing sedation and anxiolysis at a dose of 0.25 mg/kg, with minimal effects on respiration and oxygen saturation even when administered at doses as large as 1.0 mg/kg (maximum, 20 mg) as the sole sedating medication to healthy children in a supervised clinical setting.

Effects on the neonate of prednisone and azathioprine administered to the mother during pregnancy

We have reported a male infant whose mother was treated throughout pregnancy with large doses of azathioprine and prednisone for chronic renal disease. At birth, the child manifested lymphopenia, diminished thymic radiographic shadow, and low serum concentrations of immunoglobulins M and G. Cytomegalovirus (CMV) was cultured from maternal urine and from the infants urine at 10 weeks of age. The patient developed satisfactorily in the postnatal period and his immune status returned to normal. More than one year after birth the child appears to have developed adequately and, with the exception of low serum IgA concentration and persistent CMV infection, appears to have intact immunologic responses. Our observations in this patient and information derived from a literature review emphasize the need for short-and long-term clinical and laboratory evaluation of infants born to mothers who have been receiving immunosuppressive and potentially carcinogenic drugs during pregnancy.