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Biomedical subjects

M Shannon

Publications and source records attributed to M Shannon.

At least 109 records · Page 6Linked to original sources

Clinical evaluation of an acetaminophen meter for the rapid diagnosis of acetaminophen intoxication.

STUDY OBJECTIVES: To test the accuracy of a newly developed meter that determines serum acetaminophen concentration after a 30-second analysis of one drop of whole blood. DESIGN: Sixty-six blood samples from patients with known or suspected drug overdose were analyzed for the presence of acetaminophen. In all cases determination of serum acetaminophen concentration was performed simultaneously with the meter and by a reference laboratory. SETTING: Eligible patients were those who presented during a nine-month period to the emergency departments of two tertiary care hospitals (including a pediatric hospital). RESULTS: Thirty-one specimens had a laboratory-confirmed detectable acetaminophen concentration. The meter identified these toxic specimens in all cases; there were no false-negatives (sensitivity, 100%). Among the 35 specimens not containing acetaminophen, the meter invariably confirmed a nondetectable serum acetaminophen concentration (specificity, 100%). Acetaminophen measurements by the meter correlated strongly with laboratory determinations (r = .985, P less than .001). Repeated testing of one specimen documented the precision and reproducibility of the meter's analysis; mean coefficient of variation was .08 in measuring toxic acetaminophen concentrations. Drug coingestion had no significant effect on the accuracy of the meter. Instrument accuracy was maintained after more than 100 uses without recalibration. CONCLUSIONS: This meter identifies the possibility of rapid and accurate determinations of serum acetaminophen concentration. The instrument is ideally suited for patients with acetaminophen poisoning in whom expeditious and appropriate administration of antidotal therapy is desired.

Acetaminophen↗

The influence of age vs peak serum concentration on life-threatening events after chronic theophylline intoxication.

To identify risk factors for the development of seizures and cardiac arrhythmias after chronic, unintentional theophylline intoxication we monitored the clinical course of 72 consecutive patients referred to a regional poison center with chronic theophylline intoxication (serum theophylline concentration, greater than or equal to 167 mumol/L after protracted use). The median age of the sample was 47.5 years (range, 4 days to 91 years). Median peak theophylline concentration was 239 mumol/L, with a range of 167 to 722 mumol/L. A life-threatening event (LTE) occurred in 28 patients (39%) that included seizures in eight and a major cardiac arrhythmia in 22. The median peak (theophylline) of patients who had an LTE vs those who did not was 235.8 vs 238.7 mumol/L. However, the median age of patients with an LTE compared with those without an LTE was significantly greater (70.5 vs 18.0 years). Stratification of data by chronologic age revealed a stepwise increase in the frequency of LTE with advancing years: patients more than 75 years old had a 16.7-fold greater risk of LTE than patients less than 25 years old (95% confidence interval, 3.56, 77.5) despite comparable intergroup median serum (theophylline). These data suggest the primary determinant of LTEs after chronic theophylline intoxication is chronologic age. Elderly patients have an inordinately greater risk of LTE than younger patients. Peak serum theophylline concentration cannot predict which patients with chronic theophylline intoxication will have an LTE. Finally, these data indicate that theophylline should be used cautiously and with frequent monitoring of serum theophylline concentrations in elderly patients.

Age Factors↗

Hypokalemia after theophylline intoxication. The effects of acute vs chronic poisoning.

To characterize the frequency and pattern of hypokalemia (serum potassium level less than 3.5 mmol/L) after theophylline poisoning, we prospectively evaluated 88 consecutive patients with theophylline intoxication (serum theophylline concentration greater than or equal to 0.165 mmol/L). This mean admission serum theophylline concentration of this cohort was 0.331 mmol/L, with a range of 0.165 to 0.982 mmol/L. The simultaneous mean serum potassium concentration was 3.36 mmol/L (range, 2.20 to 5.80 mmol/L). Fifty-three patients (60%) were hypokalemic on hospital arrival. When, on the basis of recent ingestion, patients were separated into acute, chronic, or acute-on-chronic categories of theophylline intoxication, significant differences in serum potassium were found: Patients with acute theophylline intoxication had a mean serum potassium concentration of 2.94 mmol/L; 85% were hypokalemic. In contrast, patients with chronic theophylline intoxication had a mean serum potassium concentration of 3.83 mmol/L, with a 32% frequently of hypokalemia. These data demonstrate that hypokalemia is common after theophylline intoxication and has a significantly higher incidence after acute overdose. The difference in the frequency of hypokalemia between patients with acute vs chronic intoxication has unclear origins but may be related to the disparities in clinical course (particularly the appearance of seizures and cardiac arrhythmias) that have been observed after acute vs chronic theophylline intoxication.

Acute Disease↗

The generation of acetonemia/acetonuria following ingestion of a subtoxic dose of isopropyl alcohol.

A subtoxic dose of isopropyl alcohol was ingested by three subjects to evaluate the time to and extent of acetone generation and to explore its detection in the urine. Maximal serum isopropyl alcohol concentrations were observed by 30 minutes after ingestion of approximately 1 oz 70% isopropyl alcohol (0.4 mL/kg), but maximal serum acetone concentrations were not recorded until at least four hours postingestion. Urine tested positive (small) for acetone within three hours of ingestion using Acetest urine testing tablets (Ames Labs, Elkhart, IN). It was concluded that acetonemia occurs early after ingestion of isopropyl alcohol and increases as serum isopropyl alcohol concentrations decline. In addition, acetonuria may be qualitatively measured by three hours postingestion with rapid urine screening tests and may remain positive for 24 hours.

1-Propanol↗

Pharmacologic management of pain in children and adolescents.

In the management of chronic pain conditions, the combination of pharmacologic measures with physical and psychologic modalities becomes even more important. A pain clinic and pain consultation service are one model that facilitates this combined approach. Initial management of mild to moderate pain begins with nonopioid analgesics such as acetaminophen and NSAIDs. Persistent severe pain of a neuropathic character merits careful trials of antidepressants or anticonvulsants. Traditionally, use of opioids for chronic pain not due to cancer has been discouraged for adults as well as children. Recently, this view was challenged by reports by Portenoy and Foley and by Taub, who followed a group of adults with chronic pain due to a variety of conditions. They found that the majority of these patients, if managed with opioids on a regular schedule as part of an overall treatment program, could be made comfortable and were able to increase their level of functioning for several years. In general, dosage escalation and compulsive drug-seeking behaviors were not seen. Since this report was retrospective and did not involve children, caution must be applied in extrapolating these findings to children. For example, remarkably little is known about the effects of chronic opioid administration in childhood on growth and development. Certainly, this issue deserves further study before general recommendations can be made. It seems prudent to emphasize the importance of maximizing nonpharmacologic and nonopioid approaches in the management of chronic pain in children prior to embarking on long-term use of opioids.

Acetaminophen↗

Lead intoxication from lead-contaminated water used to reconstitute infant formula.

The lead found in drinking water can be a source of lead poisoning to young children, particularly those who consume large amounts of water. The authors describe a 13-month-old infant who was discovered to have plumbism during routine evaluation. The lead source was ultimately traced to the daily administration of powdered formula which was prepared with home tap water having a first-draw lead content of 130 parts per billion. This case suggests that whenever infants are fed powdered formula, consideration should be given to analysis of the home tap water for lead content.

Female↗

Use of urinary lead concentration in interpretation of the EDTA mobilization test.

In young children with plumbism who receive an EDTA mobilization test (EMT), the need exists for a means of interpreting inadequate or incomplete urine collections. We evaluated the ability of urinary lead concentration (UPbC), whole blood lead (PbB) and erythrocyte protoporphyrin (EP) to predict a positive EMT ratio (greater than or equal to 0.05% of EDTA dose excreted as urine lead). The results of 58 satisfactory EMT's in a group of young (aged 1-3.5 yr) lead-poisoned children were reviewed. A strong and significant correlation was found between UPbC and mobilization ratio (r = .63, p less than 0.0001). Weaker but significant correlation was also found between PbB versus mobilization ratio (r = .45, p = 0.0007) and EP versus ratio (r = .48, p = 0.0003). These data were placed into receiver-operator curves (ROC) to determine their optimal use as discriminants between children with positive versus negative mobilization tests. Ideal ROC characteristics (optimal sensitivity and specificity) were found in the use of a UPbC greater than or equal to 1.0 mcg/ml; at this cutoff a sensitivity of .80, specificity of .89 and positive predictive value of .90 were found. ROC's for PbB and EP demonstrated poor discriminating abilities. Our results suggest that in the absence of a satisfactory urine collection, urinary lead concentration serves as an acceptable indirect indicator of mobilization ratio. A urinary lead concentration of greater than or equal to 1.0 micrograms/ml most accurately identifies children who will have a positive mobilization ratio.

Child, Preschool↗

Cocaine exposure among children seen at a pediatric hospital.

The results of 1,680 consecutive urine and serum toxicologic screens from 1,120 patients, performed in a children's hospital during a 19-month period were surveyed. Among this sample, 52 (4.6%) patients had specimens that contained cocaine and/or metabolite. Fifteen specimens contained ethanol, a benzodiazepine, or a narcotic in addition to cocaine. Four patients were neonates, whereas three were infants from 1 to 7 months of age. The remaining 45 patients were adolescents with a mean age of 19 years. Among the adolescents, 11 had a significant chronic illness. In 19 patients (37%), cocaine exposure was unsuspected until the results of testing for toxic substances were known. The reasons for hospital evaluation included depression/attempted suicide in 19 patients, seizure in five, chest pain in 5, motor vehicle accident in three, syncope in three, abdominal pain in two, pneumomediastinum in two, accidental self-immolation in one, and apnea in one. Twenty patients required medical hospitalization for a total of 268 patient-days. One patient, a neonate, died. There is a striking prevalence of cocaine exposure in the pediatric age group. Among adolescents, this exposure may occur despite the presence of chronic illness. Although the age distribution appears bimodal, infants and young children may also have unsuspected exposure to this toxin. Greater awareness of cocaine exposure in childhood will be needed by primary and tertiary care pediatricians to identify affected children and provide appropriate intervention.

Adolescent↗

Serum enzyme disturbances after tricyclic antidepressant overdose.

In order to evaluate the enzymes CPK and LDH as potential biochemical markers of tricyclic antidepressant (TCA) cardiotoxicity, we prospectively followed 29 patients with TCA overdose. Serum CPK and LDH were obtained on all patients at admission. Population characteristics included a mean age of 33 y, a mean peak serum TCA concentration of 1190 ng/ml and mean maximal QRS interval of 0.10 sec. Seven patients (23%) had admission hypotension, 7 (23%) had severe respiratory depression, 6 (20%) had seizures and 4 (13%) had cardiac arrhythmias. One patient died. Mean admission CPK was 301 IU/L (nl less than 230 IU/L) while mean LDH was 221 IU/L (nl less than 250 IU/L). In 17 patients (57%), CPK remained in the normal range. There was no correlation between blood pressure, maximal QRS interval, serum TCA concentration, arrhythmias or seizures and CPK or LDH by regression analysis. CPK isoenzymes were obtained in 6 patients (both with and without severe myocardial dysfunction). One patient had an MB fraction of 10%; the remaining 5 had no measurable enzymes of myocardial origin. We conclude that modest elevations in CPK or LDH may occur after TCA overdose. These enzymes do not appear to originate from the myocardium and are of no utility in the assessment of antidepressant cardiotoxicity or prediction of clinical course.

Adolescent↗

Hypotension in severe tricyclic antidepressant overdose.

Sixty four patients who presented to the emergency department following severe acute tricyclic antidepressant (TCA) overdose (defined as an antidepressant ingestion associated with a QRS interval greater than or equal to 0.10 seconds, TCA level greater than or equal to 500 ng/mL, or grade IV coma) were prospectively evaluated to determine the incidence of hypotension and the factors associated with its development. Among these patients, the mean antidepressant level was 1,094 ng/mL. The overall frequency of admission hypotension (systolic BP less than 95 mmHg) was 34% (22 of 64 patients). Using regression analysis, systolic BP showed poor correlation with TCA level (r = -.37) and maximal QRS interval (r = -.17) following severe TCA overdose. Using multivariate analysis with a logistic regression model, the influence of BP (as well as TCA level, QRS interval, and coingestion of another drug) was evaluated on four clinical outcomes: seizures, arrhythmias, aspiration pneumonia, and pulmonary edema. The occurrence of arrhythmias and pulmonary edema was significantly associated (inversely) with hypotension (P less than .01). Seizures and aspiration pneumonia were unrelated to admission BP. These results suggest that hypotension is common after severe TCA overdose and occurs independently of TCA level and prolongation of the QRS interval. Hypotension is strongly associated with the development of arrhythmias and pulmonary edema. Seizures and aspiration pneumonia may occur regardless of initial BP.

Adult↗

Efficacy and toxicity of D-penicillamine in low-level lead poisoning.

In a retrospective cohort study we reviewed our experience using D-penicillamine in children with low-level lead poisoning (whole blood lead levels 25 to 40 micrograms/dL) to determine its efficacy and the incidence of side effects. Two groups were compared: treated subjects (n = 84) were treated with penicillamine at a mean daily dose of 27.5 mg/kg; control subjects (n = 37) received no chelation therapy. Over a prechelation observation period of 60 days, lead levels (PbB) did not change in either group. With a mean period of 76 days of D-penicillamine therapy, PbB fell in treated patients by 33% (P less than 0.001). In 64 patients (76%), PbB was reduced to a currently acceptable range (less than or equal to 25 micrograms/dL). There were eight treatment failures (10%). In control subjects, mean PbB did not change significantly over 119 days of observation. Fourteen control subjects eventually required conventional chelation with calcium disodium ethylene-diaminetetraacetic acid, and 17 were lost to follow-up. Use of D-penicillamine was associated with an adverse reaction in 28 cases (33%); transient leukopenia occurred in eight, rash in seven, transient platelet count depression in seven, enuresis in three, and abdominal pain in two. Treatment was terminated prematurely in eight cases (10%) because of an adverse reaction. We conclude that D-penicillamine is effective therapy for selected children with low-level plumbism, but adverse effects can complicate or prevent its use in some patients.

Adolescent↗

Clinical toxicity of cocaine adulterants.

Adulterants are found in all street samples of cocaine. They add an unappreciated dimension to the clinical toxicity of cocaine abuse. Identification of these adulterants is necessary to separate their effects from those of cocaine. The comprehensive toxic screen, which provides multiple modalities of drug analysis, will be a key diagnostic tool in the further investigation of these inherently toxic agents and their impact on syndromes of cocaine intoxication.

Anesthetics, Local↗

Recurrent lead poisoning in a child with immobilization osteoporosis.

Lead poisoning associated with progressive osteoporosis in patients who have been previously lead poisoned has been described but poorly documented. We managed a 4-year-old child with a prior history of plumbism who developed recurrent blood lead elevations (as high as 70 mcg/dl), requiring multiple courses of EDTA, after acute paraplegia from transverse myelitis. The patient was hospitalized throughout these periods of chelation. No exogenous sources of lead were found. Calcium, phosphate, magnesium, alkaline phosphatase and parathyroid hormone levels remained normal while vitamin D levels were depressed. Metabolic studies revealed negative calcium balance with an elevated urinary calcium:creatinine ratio. Long-bone radiographs were remarkable for progressive osteoporosis with no evidence of metallic foreign bodies. This case illustrates that bone, the major repository of lead, can become a source of significant lead level elevations in conditions associated with accelerated resorption.

Child, Preschool↗

Pulmonary consequences of severe tricyclic antidepressant ingestion.

We prospectively studied 56 consecutive patients with severe tricyclic antidepressant ingestion to determine the incidence of associated pulmonary complications. Among the patients meeting the entrance criteria, the mean antidepressant level was 1136 ng/ml. Other characteristics were a QRS duration of greater than or equal to 0.1 seconds in 35 (63%) and seizures in 19 (34%). Seventeen patients (30%) developed 18 abnormal chest X-ray findings which included pulmonary edema in 8 cases and aspiration pneumonia in 10. Using logistic regression, we evaluated the influence of tricyclic antidepressant level, blood pressure, QRS interval, seizures, drug co-ingestion and the use of gastric lavage vs. ipecac-induced emesis on pulmonary complications. For patients with pulmonary edema, the only significantly associated factor was hypotension on emergency department presentation. For aspiration pneumonia, no significant associations were found. Co-ingestion of another drug had no apparent influence on the development of pulmonary abnormalities. Our findings suggest that pulmonary edema and aspiration pneumonia are frequent complications of severe ingestions of tricyclic antidepressants. Pulmonary edema appears to result from hypotension or its treatment. The etiology of aspiration pneumonia is unclear. A chest X-ray should be obtained in all victims of tricyclic antidepressant overdose.

Administration, Oral↗