Joseph A. Weinberg

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.

Control of vasopressin secretion in the newborn lamb.

Summary: The plasma sodium, osmolality, and arginine vasopressin (AVP) responses to phlebotomy, hypertonic saline, water loading and fluid restriction were studied in 2–49 day old lambs. Phlebotomy of 10 and 20% of the lambs estimated blood volume produced 37-and 44-fold increments in plasma AVP, without a concomitant change in plasma sodium or osmolality. The infusion of 10 mEq/kg sodium chloride produced a 12% rise in plasma sodium concentration accompanied by a 7-fold rise in plasma AVP. Water loading with 100 ml/kg hypotonic fluid produced a significant fall in plasma sodium concentration (10.7%) and a decrease in plasma AVP. Eighteen hr of water deprivation evoked a 7-fold increase in AVP.These results indicate that the newborn lamb is capable of responding appropriately to known stimuli for AVP secretion. The stimulus response ratio (SRR): of newborn lambs was nearly identical after hypertonic saline and water loading and was also quite similar to that of the adult ewe after a saline challenge. The SRR of water deprived lambs was greater than that after the other stimuli, presumably reflecting combined volume and osmolar stimuli. We conclude that the neurohypophysis and the volume receptor systems of the newborn lamb are capable of appropriate, mature AVP responsiveness during the first days of extrauterine life.Speculation: The present studies indicate that AVP secretion in the newborn sheep is responsive to both volume and osmolar stimuli. Quantitative responses are equivalent to those of mature ewes. If the newborn human is both osmo- and volume sensitive, as seems likely, AVP secretion may be important in fluid and electrolyte homeostasis in the newborn period. Thus, lack of AVP secretion does not explain the limited ability to concentrate urine demonstrated by the newborn infant.

Plasma tumor necrosis factor and post-traumatic hyperdynamic sepsis evoked by endotoxin.

To examine the role of systemic plasma tumor necrosis factor (TNF) in the septic response following trauma, an endotoxin (lipopolysaccharide (LPS)) challenge was administered to anesthetized mongrel pigs 72 h following either hemorrhagic shock/resuscitation or sham shock. For TNF to be considered a mediator, at least two conditions should be satisfied: a TNF increase should precede other manifestations of the septic response and the magnitude of that increase should correlate with the symptoms. Immediately following resuscitation from shock, hemodynamics were stable, but heart rate, cardiac index (Cl), and systemic oxygen delivery (DO2) were elevated 20–60%, and systemic vascular resistance (SVR) was decreased 40%, relative to the preshock baseline. After 72 h, the animals were reanesthetized, reinstrumented, and all hemodynamic values were near normal in both groups. At this point, either 1.5 (shock, n = 2; sham, n = 2), 15 (shock, n = 7; sham, n = 6) or 150 (shock, n = 11; sham, n = 4) μg/kg of Escherichia coli LPS was administered intravenously over 30 min. Serial hemodynamic data, complete blood counts, and TNF were recorded for 3 h post-LPS. LPS evoked profound leukopenia and pulmonary hypertension within 15 min that was followed by a hyperdynamic septic response (i.e., progressive arterial desaturation, tachypnea, tachycardia, increased Cl, and decreased SVR) and rise in plasma TNF at 60–90 min. In the shock group, LPS-evoked TNF changes were less than or equal to those in the sham group, even though mortality was higher after shock. By 60 min after 15 μg/kg LPS, plasma TNF was 10 ± 2 vs. 21 ± 4 units/ml in shock vs. sham (p < .05). The corresponding mortality after 3 h was 2/7 in shock and 0/6 in sham. After 150 μg/kg LPS, plasma TNF increased to 16–18 units/ml in both groups, but the 3 h mortality was 8/11 in shock and 1/4 in sham. Since plasma TNF did not rise until after other symptoms of an LPS-evoked inflammatory response were already apparent and since the increment in plasma TNF was not potentiated by a prior bout of resuscitated shock, it is unlikely that the response evoked by a septic challenge following traumatic shock can be directly attributed to excessive levels of systemic TNF.

Physician Intervention for Improving Tobacco Control Among Parents Who Use Tobacco

Research has demonstrated that parents who smoke are often inadvertent sources of their children’s first cigarettes. Teaching parents to restrict their tobacco may give pediatricians another method for helping parents who are not ready to quit smoking. This purpose of this study was to determine the feasibility of a program training pediatricians to discuss tobacco control with smoking parents and to examine changes in parents’ tobacco control after the physician intervention. One month after the intervention by pediatricians, parents reported significantly improved tobacco control. They were more likely to count their packs and cigarettes and to keep their tobacco products at work and on their person. Parents reported restricting household control of adult smoking, and children were exposed to significantly less secondhand smoke. These results showed that it is possible to integrate advice about tobacco control into a busy pediatric practice and to improve parents’ restrictions of their tobacco products.

The Impact of Hypercarbia on the Evolution of Brain Injury in the Setting of Traumatic Brain Injury and Systemic Hemorrhage

The Impact of Hypercarbia on the Evolution of Brain Injury in the Setting of Traumatic Brain Injury and Systemic Hemorrhage

CONTROL OF VASOPRESSIN (AVP) SECRETION IN THE LAMB

The newborn is capable of secreting AVP, but there are no data regarding relative responsiveness to the several known physiological stimuli. We examined AVP, plasma sodium (Ma) and osmolality (Osm) in response to phlebotomy, water loading, hypertonic saline and mild dehydration in 7-11 lambs, 2-49 (mean = 19) days of age. AVP was measured by radioimmunoassay.Repeated phlebotomies (total 20 ml/kg) raised AVP from 4.8 ± 2.1 (mean ± SEM) to 74 ± 19 μU/ml (p < .01), while Na and Osm remained unchanged. When 100 ml/kg 2.5% dextrose/water was infused over 60 minutes, AVP fell from 3.,4 ± 1.2 to 0.7 ± 0.6 μU/ml by 60 minutes (p < .05). Na and Osm fell from 140 to 125 mEq/L and 283 to 262 mOsm/kg respectively (p < .05) Hypertonic (23%) sodium chloride infusion (10 mEq/kg) increased Na from 142 to 159 mEq/L and Osm from 271 to 318 mOsm/kg over a 30 min period (p < .05). In response to this stimulus, AVP increased from 2.9 ± 0.7 to 22.2 ± 9 μU/ml (p < .05). After 18 hours of dehydration, AVP rose from 0 6 ± 0.1 to 34 ± 1 8 μU/ml, Na from 134 to 140 mEq/L (p < 05) and Osm from 293 to 306 mOsm/kg (p < .05).Thus the newborn lamb is capable of responding to both volume and osmolar stimuli. The quantitative stimulus-response ratios (SRR = Mog AVP/ΔOsm) were similar for water loaded and saline stimulated newborns and similar to responses in the adult. The dehydration SRR was not accountable by osmolar change alone but also reflected volume change.

A NEW SYNDROME OF HYPERURICEMIA, PULMONARY FIBROSIS, AND RENAL DISEASE IN A KINDRED

A three month old male manifested failure to thrive, neurological dysfunction, moderate renal insufficiency, extreme hyperuricemia (16.5 mg%), and arterial hypoxemia and a radiographic picture compatible with idiopathic pulmonary fibrosis (IPF). A sister had died at age 6 months with IPF proven at autopsy, mild glomerular insufficiency and a disproportionate elevation in serum urate (10.6). There was no parental consanguinity nor positive family history for similar abnormalities. On a purine-free diet and 50 mg allopurinol the probands serum urate was controlled at 5.5-7 mg%. N-15 uric acid tracer was administered intravenously while continuing allopurinol. Miscible urate pool size was considerably increased (55 mg/kg). Urate turnover was 11 mg/kg/24h; this figure may reflect increased de novo purine synthesis but sufficient data on children receiving allopurinol are not available to warrant a firm conclusion. Known enzymatic causes for purine overproduction were excluded since the following activities (nmol/hr/mg prot.) in RBC hemolysates were normal: hypoxanthine-guanine phosphoribosyltransferase, 79-83 (nl. 81±13 S.D.); adenine phosphoribosyltransferase, 18-19 (nl. 21±5); phos-phoribosylpyrophosphate synthetase, 84 (nl. 66±18), with normal inhibition by ADP, GDP, and 2,3-diphosphoglycerate. We conclude that the proband and his sister are examples of a previously undescribed disease state, inherited in autosomal recessive manner.