Respiratory complications during anaesthesia in Apert syndrome.

BACKGROUND: Clinical experience with anaesthesia for a series of patients with Apert syndrome (craniosynostosis, midface hypoplasia and syndactyly) has not been reported previously. METHODS: In this review, 10 years of experience was examined at our hospital. There were 145 anaesthetics administered to 18 individuals. RESULTS: There were 16 complications (15 were perioperative wheezing) which occurred in seven patients. In four cases, surgery was cancelled due to intractable wheezing. CONCLUSIONS: We could not demonstrate any benefit from preoperative administration of nebulized albuterol. Paediatric anaesthetists should be aware of this high incidence of respiratory complications in Apert syndrome.

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.

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 Administration's 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, approximately 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.

Intravenous midazolam for sedation of children undergoing procedures: an analysis of age- and procedure-related factors.

OBJECTIVE: This study was performed to determine the doses of midazolam used for sedation during procedures in children, and the frequency of adverse events. METHODS: We performed a retrospective analysis of data collected for a prospective study of flumazenil in children who had received midazolam for a procedure (n = 91, 1-17 years). RESULTS: Practitioners used a wide range of total midazolam doses (0.03-0.6 mg/kg); mean doses ranged from 0.09 +/- 0.06 mg/kg in adolescents to 0.26 +/- 0.13 mg/kg in toddlers (P < 0.001). Opioids were also used in 84% of patients. Twenty-six percent of children with normal lungs, most of whom had received relatively high opioid doses, developed decreased oxygen saturation (as low as 65%) after sedation. Other adverse events included airway obstruction (n = 3) and vomiting (n = 1). CONCLUSIONS: The frequent choice of midazolam, usually combined with an opioid, indicates its wide acceptance. Midazolam doses were inversely related to age. The presence of vomiting, airway obstruction, and decreased oxygen saturation underlines the importance of appropriate personnel, equipment, and monitors during sedation.

A randomized clinical trial of triazolam in 3- to 5-year-olds.

Triazolam has shown promise as a sedative agent for use in pediatric dentistry. However, the efficacy of triazolam has not been previously examined in a placebo-controlled study. The present clinical trial used a two-group, randomized, double-blind study design to compare the efficacy of oral triazolam with that of a placebo. The primary hypothesis tested was that triazolam would reduce negative behaviors of pediatric dental patients compared with a placebo. A secondary hypothesis was that triazolam would increase the efficiency of dental treatment by reducing the need for time-consuming behavior management by the pediatric dentist. The subjects were 54 3- to 5-year-old children, randomly assigned to the drug and placebo groups. The active drug, 0.03 mg/kg triazolam (Halcion), or lactose placebo was given orally 30 min before dental treatment. Behavior management techniques commonly used in pediatric dentistry were used during dental treatment. A single pediatric dentist provided all of the dental treatment. The procedure included an inferior block anesthesia and careful attention to anesthesia effectiveness. All sessions were video-taped and the tapes coded for child and dentist behaviors by an independent observer. There were no statistically significant differences between the groups with respect to completion of dental treatment. There were no significant differences found in either the total time or the percent of time that the subjects exhibited disruptive movements, verbal or non-verbal distress. The total use of time in the dental chair was slightly higher in the placebo than in the drug group due to more time spent preparing the child. Contrary to preliminary reports in the literature, this investigation found little or no improvement in child behavior when triazolam was used as a sedative compared with a placebo. However, triazolam did shorten the length of dental treatment, primarily by reducing dentist time in preparing the child for the dental procedure (e.g., establishing rapport and shaping behavior).

Side effects of triazolam in children.

PURPOSE: This study examined the incidence of side effects occurring with three doses of orally administered triazolam in children undergoing restorative dental procedures. METHODS: Thirty children, aged 39-81 months, participated in the study. The children were pretested for gait ataxia, amnesia, visual acuity, stereoscopic depth perception, and diplopia during a screening session. In a subsequent appointment, children received one of three triazolam dosages (0.005, 0.015, and 0.030 mg/kg) prior to dental treatment. Dosage assignment was random and double blind. Each child received a single triazolam dosage. Tests for gait ataxia, amnesia, and visual disturbances were repeated following drug administration. RESULTS: The proportion of children experiencing ataxia, amnesia, and diplopia increased with increasing triazolam dosages. The 0.030-mg/kg triazolam dosage impaired visual acuity and stereoscopic depth perception. CONCLUSION: Triazolam produces ataxia, amnesia, and diplopia in a dose-dependent manner in children.

Pain scores in infants: a modified infant pain scale versus visual analogue.

This study describes an observational system (modified infant pain scale, MIPS) with elements from a previously published observational scale and from assessments of video-recorded infant facial expressions. It was designed to allow rapid and repeated assessments of pain in infants after brief training by an observer without pediatric experience. Forty healthy term infants (17 +/- 7 weeks) undergoing elective surgery had simultaneous independent assessment of pain using two scales: a naive observer used the MIPS and an experienced pediatric nurse used a 10-cm unmarked horizontal visual analogue scale (VAS). This validation of the MIPS included its division during analysis into partial (P-MIPS, without data on sleep or vital signs) and total scores. Infants had a broad range of MIPS scores, and the two scales categorized infants as "comfortable" or "not comfortable" with a high degree of concordance. The MIPS was easily incorporated into an infant's physical examination. We recommend its use for two-point clinical pain assessment.

Plasma levels of 2% lidocaine with 1:100,000 epinephrine with young children undergoing dental procedures.

Lidocaine levels were determined for 12 children, aged 55 to 150 mo, who received routine dental treatment, including multiple intraoral injections of 2% lidocaine (2.6 to 6.4 mg/kg) with 1:100,000 epinephrine. Peak plasma concentrations of lidocaine ranged from 0.7 to 3.8 mug/ml at 5 to 15 min postinjection. Generally accepted threshold concentrations for the onset of central nervous system toxicity are 5 to 10 mug/ml. In this study, no child approached these levels when given local anesthesia for dental procedures.

Pharmacokinetics of oral triazolam in children.

The purpose of this study was to determine the pharmacokinetic behavior of triazolam in children. Nine healthy children, aged 6 to 9 years, received oral triazolam (0.025 mg/kg suspended in Kool-Aid, Kraft General Foods, Chicago, IL) before dental treatment. Plasma triazolam concentrations were measured by gas chromatography/mass spectrophotometry at approximately 5, 15, 30, 45, 60, 90, 120, 180, and 240 minutes. A one-compartment model with first-order absorption and varying parameters was used, and estimated concentration curves were obtained for each subject. The observed peak plasma concentration was 8.5 +/- 3.0 ng/mL (mean +/- SD). The observed time to peak plasma concentration was 74 +/- 25 minutes. Elimination half-life was 213 +/- 144 minutes. Substantial recovery from signs and symptoms of clinical sedation required 180 to 240 minutes. The long duration of effect and relatively slow elimination should be noted by clinicians concerned with patient safety.

Respiratory depression after low-dose caudal morphine.

PURPOSE: To report a case of respiratory depression after a small dose of caudal morphine administered to a 15-mo-old child. CLINICAL FEATURES: A 15 mo, 9.8 kg boy underwent ureteral reimplantation with general endotracheal anaesthesia and 10 ml bupivacaine 0.25% (2.5 mg.kg-1). Ninety minutes after the bupivacaine, 0.4 mg (1 mg.ml-1, 0.4 ml, 0.04 mg.kg-1) preservative-free morphine was injected after negative aspiration. Slightly more than two hours after caudal morphine, the patient became lethargic and developed decreases in oxygen saturation (to 62%) without change in heart rate or respiratory rate. Intravenous naloxone 0.1 mg (0.01 mg.kg-1) markedly improved his level of consciousness. Racemic epinephrine was administered for treatment of coincident stridor. The patient required 11 hr continuous naloxone infusion (0.001-0.002 mg.kg-1.hr-1) in the intensive care unit. He was discharged on the second postopertive day without further complication. CONCLUSION: Respiratory depression can occur in children greater than one year of age, even when small doses of caudal morphine are used. Decreased arterial oxygen saturation and lethargy are important heralds. A normal respiratory rate despite substantial hypoxaemia argues that pulse oximetry (without supplemental oxygen where possible) has a clear advantage over impedance pneumography for electronic monitoring.

Transmucosal administration of midazolam for premedication of pediatric patients. Comparison of the nasal and sublingual routes.

BACKGROUND: Nasal transmucosal midazolam is effective for premedication of pediatric patients; however, 61-74% of these patients cry at nasal drug administration. Sublingual benzodiazepines, including midazolam, are effective in adults. The current blinded randomized study compared acceptance of and behavioral responses to transmucosal midazolam administered via the intranasal and sublingual routes. METHODS: Ninety-three patients aged 0.5-10 yr were stratified by age: 30 infants and toddlers, 0.5-2 yr; 39 preschoolers, 2.1-5 yr; and 24 school age, 5.1-10 yr. They were randomized to receive 0.2 mg/kg of midazolam in the nose or under the tongue without or with additional flavoring. For the group receiving sublingual flavored midazolam, the syringe tip was dipped in candy flavor and sugar. Duration of crying and compliance with instructions for sublingual drug administration were recorded. Hemoglobin oxygen saturation by pulse oximetry and sedation score were recorded by three observers before drug administration, at 2.5-min intervals for 10 min, at separation from parents, and during induction with halothane in O2. RESULTS: Children accepted midazolam administered via the sublingual route better than that given intranasally. In children not crying before drug administration, the frequency and duration of crying was greater following intranasal compared with sublingual administration (71% vs. 18% (P < 0.0001) and 48 +/- 56 vs. 25 +/- 49 s (P = 0.004), respectively). Lack of total compliance with instructions for sublingual administration did not alter drug effect, and there were no differences between the three study groups in maximum sedation, response to separation from parents, and behavior at induction of anesthesia; 80% displayed adequate or excellent behavior. Finally, the addition of candy flavor did not improve acceptance of or compliance with sublingual midazolam administration. CONCLUSIONS: Sublingual administration of midazolam is as effective as, and better accepted than, intranasal midazolam as a preanesthetic sedative in children.

Comparison of the safety and efficacy of intranasal midazolam or sufentanil for preinduction of anesthesia in pediatric patients.

Nasal administration of sufentanil or midazolam is effective for preinduction of pediatric patients, but there are no data on which to base a choice between them. This blinded randomized study compares behavioral and physiologic responses to sedation with one of these medications followed by inhalation or intravenous induction. Ninety-five patients aged 0.5-10 yr scheduled for elective surgery were stratified by age: 30 infants 0.5-2 yr, 38 preschoolers 2.1-5 yr, and 27 school-age children 5.1-10 yr. They were randomized to receive 0.04 ml/kg of midazolam (0.2 mg/kg) or sufentanil (2 micrograms/kg). Hemoglobin oxygen saturation by pulse oximetry (SpO2) and sedation score were recorded prior to drug administration, at 2.5-min intervals for 10 min, at separation, and during induction with graded halothane in oxygen. Intubation was performed under deep halothane or 3 mg/kg of thiopental and 0.1 mg/kg of pancuronium. Chest wall compliance was assessed qualitatively in all patients prior to intubation. To assess the effects of a mild standardized stress on unpremedicated patients, 75 of the children with parents present were scored before and after oximeter probe placement: of these, in 63% the sedation score did not change; 33% appeared more anxious; and only 4% seemed reassured. Children of all ages reacted negatively to physicians, and 23% were crying prior to administration of drugs. Sufentanil appeared less unpleasant to receive than midazolam: children cried 46 +/- 100 versus 76 +/- 73 s (P less than 0.05), respectively, but by 7.5 min, no child was crying. Median behavior scores at maximum anxiolysis were not different, but response to sufentanil was more variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Preanesthetic preparation of pediatric outpatients: the role of a videotape for parents.

Expanded outpatient surgery for pediatric patients makes it difficult to provide an unhurried and thorough preoperative visit. A useful component could be a videotape to be seen by parents at the time of their initial hospital visit. For this study, a videotape was made that included an actual induction of anesthesia procedure, information about pediatric anesthesia, and a discussion of the risks of injury or death during anesthesia. To decrease anxiety from discussion of risk, monitoring equipment was shown and explained. This survey investigated whether, after seeing the tape, the parents of children scheduled for outpatient surgery thought they were better informed and less anxious about the child's anesthetic. During a preoperative clinic visit, an interviewer introduced the tape and its purpose to 31 parents of 25 children, then asked a series of standard questions. When asked directly, most parents (74%) said the film did not change their concerns about the anesthetic, although 42% of the parents of the children with no surgical history reported decreased concern. In contrast, 84% to 97% of the parents considered seven specific aspects of the film to be helpful in reducing concern. Half were reminded of issues to be discussed with the child's anesthesiologist. Most parents (65%) appeared to accept discussion of the risk of perioperative death, although some had strongly negative reactions. The results suggest that a supportive preoperative tape can acquaint parents with the basis for anesthesiologists' concerns and facilitate the preoperative visit. Seeing an actual anesthetic may help to reassure parents about the anesthetic care their children will receive.(ABSTRACT TRUNCATED AT 250 WORDS)

Inflation-associated increases in lung polyamine uptake: role of altered pulmonary vascular flow.

Unilateral pneumonectomy in rats leads to rapid compensatory growth of the remaining lung. Previous studies showed that postoperative increases in lung mass are preceded by enhanced uptake of exogenous polyamines and by alterations in adenosine 3',5'-cyclic monophosphate (cAMP) metabolism. These effects are both mimicked in lungs of intact animals subjected to increased inflation in vitro. Partial pneumonectomy also leads to increased flow to the contralateral lung associated with reduced pulmonary vascular resistance. This raises the possibility that the postoperative metabolic response is initiated by changes in pulmonary artery pressure (Pa) or flow, rather than altered inflation. The present studies were designed to investigate this issue. Uptake of exogenous [14C]spermidine by isolated perfused rat lungs was examined over a wide range (greater than 4-fold) of pulmonary flow and ventilation at fixed PaS. Assessment of tissue metabolism from rates of protein synthesis suggested stability of the isolated lung preparations. Apnea (0 ventilation) had no effect on spermidine uptake or flow rate, compared with lungs evaluated under normal conditions of ventilation (inspiratory pressure, 15 cmH2O; positive end expiratory pressure, 2 cmH2O; rate, 70 breaths/min). At both high and low Pa (at a flow rate of 37 +/- 1 and 11 +/- 2 ml/min, respectively, with 0 ventilation), removal of the left lung from the perfusion circuit increased specific right lung flow rate greater than 30% but had no effect on spermidine uptake. Similar alterations in flow rate to the right or both apneic lungs had no effect on the tissue content of cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Minimizing perioperative hypoxemia does not affect postpneumonectomy lung growth.

The effects of preventing the acute hypoxemia common during lung resection on postpneumonectomy lung growth were investigated. Rats that had undergone translaryngeal tracheal intubation and were supported with intermittent positive-pressure ventilation during pneumonectomy (IPPV) were compared with those allowed to breathe room air spontaneously via the natural airway (SV). A pulse oximeter was used to document intraoperative and postoperative oxygen saturation (SaO2). Almost all SV animals became acutely hypoxemic during thoracotomy [SaO2 less than 50% for 2.5 +/- 0.5 min (8/9), less than 30% for 1.7 +/- 0.4 (8/9)], whereas IPPV animals largely maintained oxygenation [SaO2 less than 50% for 0.3 +/- 0.2 min (8/13), less than 30% for 0.05 +/- 0.05 min (1/13)]. Direct measurements of oxygen saturation correlated well with the pulse oximeter (slope of regression line = 0.90, correlation 0.91), and arterial blood gases showed the SV group to be hypercapneic and acidotic as well as hypoxemic during lung removal. These abnormalities resolved soon after chest closure. Intubated animals had mild postextubation hypoxemia that normalized within 3 h of surgery. Two weeks postoperative, there were no differences in lung mass or content of water, RNA, DNA, and protein between the two groups.

Control of compensatory lung growth by adrenal hormones.

The effects of adrenalectomy and/or in vivo treatment with hydrocortisone acetate (HCA;5 mg X kg-1 X day-1) on lung growth were investigated in control and pneumonectomized rats of 250 g body wt. Left pneumonectomy (day 0) initiated rapid hyperplastic growth of the right lung, which was unaffected by HCA. Similarly, HCA had no effect on lung growth in unoperated control animals. Two weeks after pneumonectomy, right lung dry mass, protein, RNA, and DNA were equal to that in both lungs of unoperated rats. Adrenalectomy 5 days before (day -5) left pneumonectomy increased the rate and extent of right lung growth, but did not change its hyperplastic character. Continuous HCA treatment (days -5 to 14) prevented the adrenalectomy-mediated increase in postpneumonectomy lung growth. "Early" HCA dosing (days -5 to 6) of adrenalectomized-pneumonectomized animals suppressed lung growth to the pneumonectomy level, but from days 7 to 14 growth accelerated to the adrenalectomized-pneumonectomized rate. Conversely, "late" HCA, initiated when adrenalectomized-pneumonectomized animals had restored normal total lung mass (days 6 to 14), quickly reduced right lung growth to rates typical of unoperated controls. The latter effects were not observed unless continuous steroid treatment was provided throughout this interval. The data support a role for glucocorticosteroids in modulation of the accelerated compensatory lung growth initiated by partial resection of the tissue.