Hepatotoxicity in acute iron poisoning.

Although liver injury is a recognized consequence of acute iron poisoning, its description is limited to several case reports. It appears to be dose-related, however, there are published reports of severe iron poisoning without liver injury. The purpose of this study is to examine the hypothesis that this is a dose-related phenomenon and to identify the serum iron concentration of risk for this outcome. The design of this study is a retrospective review of our hospital's experience over 20 years. Extracted data included demographics, time of ingestion, highest serum iron concentration and highest hepatic transaminase activity. Iron poisoning was defined as a serum iron concentration >300 microg/dL (55 micromol/L) within 12 hours of ingestion. Hepatotoxicity was defined as a serum transaminase (either ALT or AST) >150 U/L. Severe hepatotoxicity was defined >1000U/L. Seventy-three patients (1-48 years old) participated in the study and of these patients 60 (47 female) did not have hepatotoxicity. Their serum iron concentrations were 300-704 microg/dL (55-128 micromol/L). Thirteen patients had hepatotoxicity and of these patients, nine had severe liver injury. Severe injury was associated with serum iron concentrations well in excess of 1000 microg/dL (182 micromol/L). Our data support hepatotoxicity due to iron poisoning as a dose-related phenomenon with clinically important cases unlikely with a serum iron concentration of < 700 microg/dL (128 micromol/L) within the first 12 hours. Clinically important hepatotoxicity occurs with values in excess of 1000 microg/dL (182 micromol/L).

Long term effects of a home visit to prevent childhood injury: three year follow up of a randomized trial.

OBJECTIVE: To assess the long term effect of a home safety visit on the rate of home injury. DESIGN: Telephone survey conducted 36 months after participation in a randomized controlled trial of a home safety intervention. A structured interview assessed participant knowledge, beliefs, or practices around injury prevention and the number of injuries requiring medical attention. SETTING: Five pediatric teaching hospitals in four Canadian urban centres. PARTICIPANTS: Children less than 8 years of age presenting to an emergency department with a targeted home injury (fall, scald, burn, poisoning or ingestion, choking, or head injury while riding a bicycle), a non-targeted injury, or a medical illness. RESULTS: We contacted 774 (66%) of the 1172 original participants. A higher proportion of participants in the intervention group (63%) reported that home visits changed their knowledge, beliefs, or practices around the prevention of home injuries compared with those in the non-intervention group (43%; p<0.001). Over the 36 month follow up period the rate of injury visits to the doctor was significantly less for the intervention group (rate ratio = 0.74; 95% CI 0.63 to 0.87), consistent with the original (12 month) study results (rate ratio = 0.69; 95% CI 0.54 to 0.88). However, the effectiveness of the intervention appears to be diminishing with time (rate ratio for the 12-36 month study interval = 0.80; 95% CI 0.64 to 1.00). CONCLUSIONS: A home safety visit was able to demonstrate sustained, but modest, effectiveness of an intervention aimed at improving home safety and reducing injury. This study reinforces the need of home safety programs to focus on passive intervention and a simple well defined message.

Interaction between N-acetylcysteine and activated charcoal: implications for the treatment of acetaminophen poisoning.

STUDY OBJECTIVE: To determine if the presence of N-acetylcysteine reduces the ability of activated charcoal to adsorb acetaminophen both in the absence and presence of a coingestant. DESIGN: In vitro laboratory study. SETTING: University hospital research laboratory. MEASUREMENTS AND MAIN RESULTS: The adsorption of acetaminophen and salicylic acid by activated charcoal in the presence and absence of N-acetylcysteine was measured in vitro. Acetaminophen and salicylic acid analyses were conducted with high-performance liquid chromatography. Adsorption data were compared using the appropriate parametric statistical test. The addition of N-acetylcysteine significantly decreased the binding of acetaminophen by activated charcoal (p<0.005). When salicylic acid was added to simulate a coingestant, N-acetylcysteine significantly decreased salicylate adsorption by charcoal (p<0.001). CONCLUSIONS: The presence of N-acetylcysteine reduces the ability of activated charcoal to adsorb acetaminophen and coingestants. In vivo data will be required to determine the clinical relevance of these interactions.

The effectiveness of a home visit to prevent childhood injury.

OBJECTIVE: To examine the effectiveness of a home visit program to improve home safety and decrease the frequency of injury in children. We examined the effects of the program on 1) parental injury awareness and knowledge; 2) the extent that families used home safety measures; 3) the rate of injury; and 4) the cost effectiveness of the intervention. DESIGN: A randomized, controlled trial. SETTING: A multicenter trial conducted at 5 hospitals in 4 Canadian urban centers. PARTICIPANTS: Children <8 years old, initially enrolled in an injury case-control study, were eligible to participate. Intervention. Subsequent to a home inspection conducted to determine baseline hazard rates for both groups, participants in the intervention group received a single home visit that included the provision of an information package, discount coupons, and specific instruction regarding home safety measures. MAIN RESULTS: The median age was 2 years, with males comprising ~60% of participants. The experimental groups were comparable at outset in terms of case-control status, age, gender, and socioeconomic status. Parental injury awareness and knowledge was high; 73% correctly identified injury as the leading cause of death in children, and an intervention effect was not demonstrated. The adjusted odds ratios (ORs) for the home inspection items indicated that significant safety modifications only occurred in the number of homes having hot water not exceeding 54 degrees C (OR: 1.31, 95% confidence interval [CI]: 1.14, 1.50) or the presence of a smoke detector (OR: 1.45, 95% CI: 0.94, 2.22). However, the intervention group reported home safety modifications of 62% at 4 months and significantly less injury visits to the doctor compared with the nonintervention group (rate ratio: 0.75; 95% CI: 0.58, 0.96). The total costs of care for injuries were significantly lower in the intervention group compared with the nonintervention group with a cost of $372 per injury prevented. CONCLUSIONS: An intervention using a single home visit to improve the extent to which families use safety measures was found to be insufficient to influence the long-term adoption of home safety measures, but was effective to decrease the overall occurrence of injuries. Future programs should target a few, well-focused, evidence-based areas including the evaluation of high-risk groups and the effect of repeated visits on outcome.

Pediatric trauma registries: the foundation of quality care.

BACKGROUND/PURPOSE: Traumatic injuries cause substantial morbidity and mortality in children. Trauma registries are essential to assess and improve standards of trauma care. An interprovincial study of pediatric trauma between 6 centers across Canada who use identical software components was completed. METHODS: Data were collected from April 1, 1995 to December 31, 1998 for children aged 1 day to 17 years with an injury severity score of > or = 12. Cause of injury, injury time and day, gender, age, injury scores, length of hospital stay, and outcomes were compared. RESULTS: A total of 1,276 patients were included. Mean age was 10.3 +/- 5.6 years. Motor vehicle collisions were the most common mechanism of injury (56%). Boys were more often injured (66%; P < .05). Injuries occurred mainly between 1600 and 2400 hours (P < .0001). Mean hospital stay was 11.5 +/- 16.6 days. The longest stays in the hospital were among those who had an abdominal abbreviated injury score (AIS) of 1 (P < or = .03). Patients with similar injury severities remained twice as long in Winnipeg Children's Hospital (hospital 5), hospital 2, and hospital 6 as compared with patients in hospital 3 (P < .05). Differences existed in discharge placement between hospitals (P < .0001). CONCLUSIONS: This study was the first to compare pediatric patients in multiple Canadian centers using identical trauma registries. Variations in length of stay and discharge placements between hospitals were identified. Further analysis of data in the registries may clarify these differences and serve as a foundation for hospitals to improve the quality of patient care.

Hepatotoxicity in acute iron poisoning.

Although hepatotoxicity is a known sequela of acute iron poisoning, the literature describing it is confined to sporadic reports. Key issues such as prognosis and whether this is a dose-related phenomenon are not addressed. Review of this literature and of experimental animal studies demonstrates that it occurs early in the clinical course and has a relatively high mortality. The lowest acute serum iron concentration associated with hepatotoxicity was 1700 microg/dL (304 micromol/L). Since this greatly exceeds the reference range of 50-150 microg/dL (9-27 micromol/L), it supports a dose-related etiology. Unlike most other hepatotoxins, the periportal areas of the hepatic lobule are the primary sites of injury. As this is the principle sitefor hepatic regeneration, this accountsfor the relatively high mortality rate. An understanding of the pathogenesis of the hepatotoxicity of acute iron poisoning is central to the identification of rational and effective interventions. From the clinical perspective, the relatively high mortality rate of iron poisoning-induced hepatotoxicity requires vigilance for its onset and earlier consideration of liver transplantation.

How long after drug ingestion is activated charcoal still effective?

OBJECTIVE: The recent American Academy of Clinical Toxicology/European Association of Poisons Centres and Clinical Toxicologists position statement on activated charcoal stated "there are insufficient data to support or exclude its use after 1 hour of ingestion.'' The purpose of this study was to determine the effectiveness of activated charcoal administered 1, 2, and 3 hours after drug ingestion. METHODS: This was a human volunteer, randomized crossover study. Ten volunteers ingested 4 g of acetaminophen on four occasions at least 1 week apart. One ingestion served as a control and the other three as experimental ingestions with charcoal being administered at 1, 2, and 3 hours after acetaminophen dosing. Eight blood specimens were obtained over the initial 8 hours for serum acetaminophen concentrations that were used for calculation of routine pharmacokinetic parameters. Repeated measures of ANOVA and Tukey's HSD test were used for statistical analysis. RESULTS: Pharmacokinetic parameters for acetaminophen in our volunteers were consistent with literature values. The mean area under the curve (AUC+/-SD) for the control and the 1-, 2-, and 3-hour groups were 221 +/- 54, 154 +/- 71, 206 +/- 67 and 204 +/- 58 mg/L/h, respectively. The 1-hour group was the only one differing from control (p < 0.01). The decrease of bioavailability at 1 hour was 30.3%, which is similar to previous studies. CONCLUSION: Our data do not support the administration of activated charcoal as a gastrointestinal decontamination strategy beyond 1 hour after drug overdose.

Variation in utilization of computed tomography scanning for the investigation of minor head trauma in children: a Canadian experience.

OBJECTIVES: To compare the utilization rates of CT scans in investigating minor head trauma in children in Canada, to identify the injuries determined by these scans, and to identify clinical findings that are highly associated with its diagnosis and the injury itself. METHODS: A retrospective cohort study involving nine pediatric hospitals in Canada was conducted. A structured data collection method was used. Inclusion criteria included age 16 years or less, history of blunt head trauma, and a Glasgow Coma Scale score (GCS) greater than or equal to 13. Data collected included demographic information, type of injury, relevant clinical information, computed tomography (CT) scan data, and clinical outcome. Clinical findings associated with CT scan and positive CT scan were identified using logistic regression. RESULTS: One thousand one hundred sixty-four children were included in the study. One hundred seventy-one (15%) had a CT scan, of which 60 (35%) were abnormal. There was a significant difference in the rate of ordering of CT scans among the participating hospitals, but no significant difference in the rate of abnormal CT scans. Mechanism of injury, GCS, and loss of consciousness were significantly related to the presence of an abnormal CT scan. CONCLUSIONS: Although there is a significant difference in the utilization of CT scans to investigate minor head trauma in children across Canada, there is no significant difference in the frequency of head injuries in these patients. This suggests that it may be possible to determine clinical criteria that are predictive of a head injury in these patients.

Emergency department management of pediatric migraine.

Migraine is a common pediatric emergency department problem. Since its pathophysiology is unclear and possibly multifactorial, a single treatment strategy is unlikely to be successful for all patients. A specific treatment that has been successful for a particular patient should be strongly considered. Otherwise, it is best to start with simple therapies such as acetaminophen, aspirin, or an NSAID if not already tried at home. For patients requiring more specific therapy, reasonable choices would be dihydroergotamine or a dopamine antagonist such as prochlorperazine. There are several newer agents studied in adults with examples being sumatriptan and naratriptan. These probably have a role in the adolescent and should be considered in the younger age group when other therapies have failed. When the headache has been prolonged, dexamethasone may be useful in decreasing inflammation and relieving pain. As illustrated in many of the above studies, monotherapy is often inadequate in achieving complete relief of headache pain in all patients. Most of the drugs discussed here address only one of the three etiologies thought to be involved in migraine pathogenesis, namely; the dopaminergic system. the serotonin system or inflammation. Presumably, therapy directed toward more than one of these etiologies at the same time may be more effective (11).

Vaccination of emergency department patients at high risk for influenza.

OBJECTIVE: To determine the proportion of Canadian emergency department (ED) patients who are at risk for increased morbidity from influenza but were not vaccinated and to determine emergency physicians' (EPs') willingness to screen for and prescribe influenza vaccination. METHODS: The authors surveyed a convenience sample of patients presenting during a one-week period at each of four EDs in Winnipeg, Manitoba, Canada, after the end of the seasonal period for vaccination. They also surveyed all full-time EPs in Winnipeg. RESULTS: Fifty-three percent of emergency patients at risk for increased morbidity from influenza had not been vaccinated and 59.3% of them were willing to be vaccinated during an emergency visit. This represents 31.6% (+/-3.1%) of all high-risk patients and 15% of all emergency patients. High-risk patients who did not have a regular physician were less likely to have been vaccinated (OR 0.165, p = 0.018). Most EPs rarely or never offer influenza vaccination (30% and 57%, respectively). Seventy-six percent of them were willing to prescribe vaccination. CONCLUSION: Many ED patients are at risk for increased morbidity from influenza and have not been vaccinated. The majority of them are willing to be vaccinated during an emergency visit and the majority of EPs are willing to prescribe vaccination. Emergency department vaccination for influenza should be considered as a strategy to increase vaccination among high-risk groups.

Childhood diethylene glycol poisoning treated with alcohol dehydrogenase inhibitor fomepizole and hemodialysis.

Diethylene glycol (DEG), a commonly used solvent, has been implicated in multiple poisoning deaths, the most recent being the Haitian acetaminophen tragedy. Unlike the more commonly seen ethylene glycol ingestion, little is understood of DEG metabolism or kinetics in humans. This has made the clinical presentation, biochemical correlates, and treatment options unclear. Patients presenting less than 12 hours after DEG ingestion may not show metabolic acidosis, whereas those presenting later may show florid metabolic acidosis. Kinetic data lend support to these observations. We report a case of DEG ingestion in a 17-month-old girl who was managed with activated charcoal, fomepizole (a recently available alcohol dehydrogenase inhibitor), and hemodialysis (HD). Pre-HD and post-HD DEG levels support clearance of DEG with HD.

Gastric lavage for liquid poisons.

STUDY OBJECTIVE: This study was conducted to determine whether gastric lavage reduces the absorption of ingested liquids. METHODS: The study design was a randomized controlled human volunteer crossover study in 10 subjects. On 2 separate occasions 2 weeks apart, the volunteers ingested a solution of 4.0 g of acetaminophen in 60 mL of water. Eight blood specimens were obtained over the initial 8 hours for determination of serum acetaminophen concentrations, which were used to calculate routine pharmacokinetic parameters. One hour after 1 drug ingestion, gastric lavage was performed through a 34-F orogastric tube. Serum acetaminophen concentrations were measured by high-performance liquid chromatography and a 2-tailed t test was used for statistical analysis. RESULTS: The mean values for area under the concentration curve (+/-SD) for the control and gastric lavage groups were 195+/-31 and 154+/-52 mg/L.hour, respectively (P <.05). The mean reduction in acetaminophen bioavailability because of gastric lavage was 20%+/-28% (95% confidence interval 3 to 37). CONCLUSION: In this experimental model for the ingestion of liquids, gastric lavage at 1 hour resulted in a significant decrease in the mean serum bioavailability of acetaminophen. Nonetheless, this treatment effect is unlikely to be of clinical value because of its modest extent, unreliable performance, and the availability of a more effective, less risky alternative, activated charcoal.

Hepatotoxicity from castor bean ingestion in a child.

BACKGROUND: Castor beans contain ricin, one of the most toxic substances known. A biphasic toxicity is described consisting of acute and potentially fatal gastroenteritis followed by damage to the viscera several days later. However, the most current review of the literature states that the above delayed toxicity has not been reported. CASE REPORT: We report a 20-month-old girl with no gastrointestinal symptoms who developed reversible hepatotoxicity beginning 48-72 hours after the ingestion of castor beans. CONCLUSION: It seems prudent to follow for several days any patients who actually chewed castor beans before ingestion.

American Academy of Pediatrics. Committee on Injury and Poison Prevention. Safe transportation of newborns at hospital discharge.

All hospitals should set policies that require the discharge of every newborn in a car safety seat that is appropriate for the infant's maturity and medical condition. Discharge policies for newborns should include a parent education component, regular review of educational materials, and periodic in-service education for responsible staff. Appropriate child restraint systems should become a benefit of coverage by Medicaid, managed care organizations, and other third-party insurers.

American Academy of Pediatrics. Committee on Injury and Poison Prevention. Transporting children with special health care needs.

Children with special health care needs should have access to proper resources for safe transportation. This statement reviews important considerations for transporting children with special health care needs and provides current guidelines for the protection of children with specific health care needs, including those with a tracheostomy, a spica cast, challenging behaviors, or muscle tone abnormalities as well as those transported in wheelchairs.

Validation of the Ottawa Ankle Rules in children with ankle injuries.

OBJECTIVES: The Ottawa Ankle Rules (OAR) have been found to be 100% sensitive in adult patients with ankle injuries, and application of the OAR has resulted in a 28% reduction in the number of x-rays ordered. The objectives of this study were to determine the sensitivity and specificity of the OAR in children and to determine the potential change in x-ray utilization. METHODS: Children, aged 2-16 years, presenting to the EDs of two children's hospitals, with an ankle injury in the previous 48 hours, were enrolled. All patients were assessed by either staff physicians or fellows. X-rays were ordered according to standard clinical practice. Prior to reviewing x-rays, the physical examination was recorded on a standardized form. Positive outcomes (clinically significant) were defined as fractures with fragments > or =3 mm. Patients not x-rayed and asymptomatic at five to seven days postinjury were considered to have no significant fracture. RESULTS: Six hundred seventy patients were enrolled. The OAR were 100% sensitive (95% CI = 95% to 100%) for significant ankle fractures, with a specificity of 24% (95% CI = 20% to 28%). The OAR were 100% sensitive (95% CI = 82% to 100%) for the midfoot, with a specificity of 36% (95% CI = 29% to 43%). If the OAR had been followed, there would have been a reduction of ankle x-rays by 16% and foot x-rays by 29% without missing any clinically significant fracture. However, analysis of the two hospitals showed that if the rules had been applied, one would have a reduction in x-rays, while the other center would have an increase. CONCLUSIONS: This study demonstrates the OAR to be sensitive for detecting clinically significant (> or =3 mm) ankle and midfoot fractures in children. The application of these rules may reduce the number of x-rays ordered. A further study is required to determine the effect of using the OAR in clinical practice.

House fire injury prevention update. Part II. A review of the effectiveness of preventive interventions.

OBJECTIVE: To evaluate and summarize the house fire injury prevention literature. METHODS: MEDLINE (1983 to March 1997) was searched by keyword: fire, burn, etiology, cause, prevention, epidemiology, and smoke detector/alarm. ERIC (1966 to March 1997) and PSYCLIT (1974 to June 1997) were searched by keyword: as above, and safety, skills, education, and training. Other sources included references of retrieved publications, review articles, and books; Injury Prevention hand search; government documents; and internet sources. Sources relevant to residential fire injury prevention were selected, evaluated, and summarized. RESULTS: Forty three publications were selected for review, including seven randomized controlled trials, nine quasiexperiments, two natural experiments, 21 prospective cohort studies, two cross sectional surveys, one case report, and one program evaluation. These studies examined the following types of interventions: school (9), preschool (1), and community based educational programs (5); fire response training programs for children (7), blind adolescents (2), and mentally retarded adults (5) and children (1); office based counseling (4); home inspection programs (3); smoke detector giveaway campaigns (5); and smoke detector legislation (1). CONCLUSIONS: This review of house fire prevention interventions underscores the importance of program evaluation. There is a need for more rigorous evaluation of educational programs, particularly those targeted at schools. An evidence based, coordinated approach to house fire injury prevention is critical, given current financial constraints and the potential for program overload for communities and schools.

Inhalant abuse and the abuse of other drugs.

AIMS: To examine the relationship between inhalant abuse and other substances of abuse. DESIGN: Survey using a structured interview administered by a single trained interviewer. SETTING: A juvenile detention facility. PARTICIPANTS: 209 children incarcerated at the facility over a 3-month period. SELECTION PROCEDURE: Consecutive sample. INTERVENTIONS: None. MEASUREMENTS/FINDINGS: The structured interview was adapted from the American Drug and Alcohol Survey, which has been extensively used to obtain substance abuse epidemiologic data. We collected information on inhalants, alcohol, marijuana, downers, pep pills, lysergic acid diethylamide (LSD), cocaine, designer drugs, phencyclidine (PCP), Talwin and Ritalin, speed, and narcotics. The chi-square or Fisher exact test were used when appropriate. Mean ages of initial experimentation were as follows: inhalants, 9.7 years; marijuana, 11.9 years; alcohol (inebriated), 12.0 years; cigarettes, 11.2 years; for the remaining substances of abuse, the mean age was 13.2-14.7 years. Thirty subjects had used inhalants. Significant relationships were found between inhalants and cocaine (p = .004), Talwin and Ritalin (p = .001), downers (p = .01), and narcotics (p = .003). CONCLUSIONS: For children incarcerated in a juvenile detention facility in our community, inhalant abuse is associated with the later use of other substances of abuse. If this finding is replicated in other populations, it underscores the need for effective preventive strategies.

House fire injury prevention update. Part I. A review of risk factors for fatal and non-fatal house fire injury.

OBJECTIVE: To summarize house fire injury risk factor data, using relative risk estimation as a uniform method of comparison. METHODS: Residential fire risk factor studies were identified as follows: MEDLINE (1983 to March 1997) was searched using the keywords fire*/burn*, with etiology/cause*, prevention, epidemiology, and smoke detector* or alarm*. ERIC (1966 to March 1997) and PSYCLIT (1974 to June 1997) were searched by the above keywords, as well as safety, skills, education, and training. Other sources included: references of retrieved publications, review articles, and injury prevention books; Injury Prevention journal hand search; government documents; and internet sources. When not provided by the authors, relative risk (RR), odds ratio, and standardized mortality ratios were calculated, to enhance comparison between studies. RESULTS: Fifteen relevant articles were retrieved, including two case-control studies. Non-modifiable risk factors included young age (RR 1.8-7.5), old age (RR 2.6-3.6), male gender (RR 1.4-2.9), non-white race (RR 1.3-15.0), low income (RR 3.4), disability (RR 2.5-6.5), and late night/early morning occurrence (RR 4.1). Modifiable risk factors included place of residence (RR 2.1-4.2), type of residence (RR 1.7-10.5), smoking (RR 1.5 to 7.7), and alcohol use (RR 0.7-7.5). Mobile homes and homes with fewer safety features, such as a smoke detector or a telephone, presented a higher risk of fatal injury. CONCLUSIONS: Risk factor data should be used to assist in the development, targeting, and evaluation of preventive strategies. Development of a series of quantitative systematic reviews could synthesize existing data in areas such as house fire injury prevention.