Peter G. Lacouture

Acute isopropyl alcohol intoxication: Diagnosis and management

Alcohol intoxication (methyl, ethyl, isopropyl, and ethylene glycol) is treated frequently in emergency room and intensive care units. Although high morbidity and mortality rates exist, effective therapies for methyl alcohol and ethylene glycol (ethyl alcohol blocking and hemodialysis) and ethyl and isopropyl alcohol (hemodialysis) are available. Prompt and accurate clinical and laboratory differentiation is needed to optimize these therapies. This review presents clinical, pharmacologic, and management data, contrasts important aspects in differential diagnosis, and suggests an appropriate approach to management of isopropyl alcohol intoxication.

Effect of nifedipine on constriction of human tracheal strips in vitro

1 Autopsy specimens of human trachealis muscle were used to investigate the effect of the calcium channel blocker, nifedipine, on airway smooth muscle constriction. With these tracheal strips, two consecutive cumulative concentration‐effect curves to histamine (0.1–100 μm) obtained at a 60 min interval were highly reproducible. 2 We examined the effects of adding nifedipine (2.9 μm) to the incubation medium before the second histamine response. The concentration‐effect relationships determined after nifedipine incubation were significantly different from control: the response to 100 μm histamine was reduced by approximately one‐half (to 2.53 ± 0.6 g; P < 0.025), and the concentration of histamine causing 40% of the maximal control contraction (EC40) increased nearly ten fold (to 36.9 ± 10.5 μm; P < 0.02). 3 In two additional tracheal strips submaximally constricted with 10 μm histamine, nifedipine 2.9 μm caused complete relaxation to resting tension or below. 4 These results indicate a direct inhibitory effect of nifedipine on airway smooth muscle constriction and partial dependence of human trachealis muscle on calcium ion fluxes for initiation and maintenance of contraction. In addition, the results suggest a potential mechanism for the inhibitory effects of calcium channel blocking drugs in exercise‐induced asthma.

Monitoring cyanide and thiocyanate concentrations during infusion of sodium nitroprusside in children

SummaryOver a 19-month period, all requests for blood cyanide and/or serum thiocyanate concentrations to the Clinical Laboratory of The Childrens Hospital, Boston, were reviewed in order to determine how physicians screen for nitroprusside-related toxicity. During that period, 52 patients receiving nitroprusside were monitored for cyanide and/or thiocyanate toxicity. Overall, there were 62 cyanide and 86 thiocyanate determinations. None of the thiocyanate determinations and five of the cyanide concentrations were within the toxic range as established by the reference laboratory, and no patient displayed signs or symptoms of toxicity which could not also be explained by their underlying illness. Our findings suggest that while physicians are concerned with nitroprusside toxicity in children, there exists no apparent consensus as to how to monitor for this toxicity. The results also indicate that the relationship between blood cyanide or serum thiocyanate concentrations and clinical evidence of toxicity is not straightforward and requires further delineation.

A study of adverse reaction algorithms in a drug surveillance program

To improve agreement among observers, several investigators have recently proposed methods (algorithms) to standardize assessments of causality for presumed adverse drug reactions. We evaluated one such method in the context of an intensive pediatric drug surveillance program. Four observers rated 50 randomly selected case reports drawn from the program, first using only general guidelines and then, several months later, using the strict criteria of the algorithm. Agreement among observers was poor in both study phases. The presence of selected characteristics of adverse events (e.g., major severity) did not improve agreement in either phase of the study. We conclude that routine use of such algorithms in drug surveillance programs is not likely to be of benefit.

The adsorption of salicylates by a milk chocolate-charcoal mixture.

STUDY OBJECTIVE To evaluate the adsorptive capacity of a milk chocolate-charcoal mixture to aspirin, compared with superactivated charcoal and conventional activated charcoal. DESIGN A prospective, randomized, crossover study. SETTING The Massachusetts Poison Control Center office in The Childrens Hospital, Boston. TYPE OF PARTICIPANTS Six healthy adult volunteers with no known allergies to aspirin or chocolate, bleeding disorders, or peptic ulcer disease. INTERVENTIONS Each participant ingested 975 mg of crushed aspirin on separate days, followed by either water; 10 g milk chocolate-charcoal mixture; 10 g SuperChar Liquid; or 10 g Actidose Aqua activated charcoal. Total serum salicylate concentrations were determined by high-performance liquid chromatography at zero, one, two, four, eight, and 24 hours after ingestion. MEASUREMENTS AND MAIN RESULTS Neuman-Keuls analysis was used to measure time-to-peak concentration, which was reduced by SuperChar Liquid, 67%; milk chocolate-charcoal mixture, 106%; and activated charcoal, 56%. Aspirin absorption was calculated using Neuman-Keuls analysis to measure area under the concentration-time curve. Total aspirin absorption was reduced by SuperChar, 67%; milk chocolate-charcoal mixture, 50%; and activated charcoal, 2%. There was no difference in serum salicylate concentrations between SuperChar and milk chocolate-charcoal mixture at all time intervals. Also, all serum salicylate concentrations with milk chocolate-charcoal mixture were consistently lower than with activated charcoal. CONCLUSION Although the formulation of milk chocolate with activated charcoal reduces its adsorptive capacity compared with superactivated charcoal, it is still able to bind aspirin effectively and is superior to conventional activated charcoal. Further research may improve the binding and palatability of milk chocolate-charcoal mixture, especially for home use.

Poisoning exposures and use of ipecac in children less than 1 year old

Poison exposures in children less than 1 year old and the safety and efficacy of syrup of ipecac in children 9 to 12 months old were evaluated in a prospective eight-month study conducted at the Massachusetts Poison Control Center. Poison exposures in children less than 1 year old represented approximately 9% of the 38,080 calls received. Mobile children (in walkers, crawling, or walking) were at the greatest risk of poisoning. The majority of children (94%) were asymptomatic and none were hospitalized or died. The products involved were primarily plants (38%) and household products (30%). All 21 patients, ages 9 to 12 months, were given 10 mL syrup of ipecac under medical supervision and vomited within one hour. The mean time to vomit was 21.7 (SEM +/- 2.8) minutes. The patients vomited 3.3 (SEM +/- 0.3) times and all episodes of vomiting abated by 26.4 (SEM +/- 6.6) minutes. No significant side effects were noted. The use of the syrup of ipecac in the 9- to 12-month-old child appears to be safe and effective.

Vancomycin-associated shock and rash in newborn infants

Vancomycin, an antibiotic isolated from Streptomyces ~rientalis, was developed to treat staphylococcal infections resistant to the penicillins. However, because intravenous administration was associated with venous irritation, vancomycin was largely replaced by semisynthetic penicillins. Recently, intravenously administered vancomycin has come into increasing use, and its indications now include infections caused by Staphylococcus epidermidis and resistant Staphylococcus aureus.1 Vancomycin has become an important antibiotic for use in premature newborn infants, because S. epidermidis is the most common nosocomial infection in the neonatal intensive care unit. 2,3 Adverse reactions attributed to vaneomycin have been described in adults and children, but not in newborn infants. We report two newborn infants who had shock and rash after receiving vancomycin; these reactions were identified by tt~e Pediatric Drug Surveillance (PeDS) Program at the Childrens Hospital, Boston. 4

Serum magnesium concentrations after repetitive magnesium cathartic administration

Severe hypermagnesemia has been reported by several authors after multiple doses of magnesium-containing cathartic are administered during management of a toxic ingestion. To evaluate the frequency and magnitude of serum magnesium elevations after the use of repetitive magnesium catharsis, we prospectively evaluated 102 patients who received multiple doses of magnesium citrate as a part of treatment of an overdose. Commonly ingested substances for which repetitive cathartic was administered were tricyclic antidepressants in 47%, aspirin in 17%, and phenytoin in 10%. For each case, serial electrolytes, blood urea nitrogen, creatinine, calcium and magnesium were obtained. Mean initial serum magnesium concentration was 1.8 +/- .03 mEq/L. After a mean 960 mL of magnesium citrate (9.22 g magnesium), final mean serum magnesium concentration was 2.5 +/- .05 mEq/L. Forty-seven patients (47%) developed an elevated (greater than 2.4 mEq/L) serum magnesium concentration, with 12 greater than 3.0 mEq/L. No correlation was found between total quantity of magnesium citrate administered and the increment in serum magnesium concentration. Our data indicate that serum magnesium concentrations consistently rise after repetitive magnesium citrate use. However, the magnitude of this rise appears modest. The elevation in serum magnesium concentration does not correlate with the quantity of magnesium administered. We conclude that with close monitoring, repetitive magnesium citrate can be administered without inducing severe hypermagnesemia (serum magnesium concentration greater than 5.0 mEq/L).

Serum osmolality in alcohol ingestions: Differences in availability among laboratories of teaching hospital, nonteaching hospital, and commercial facilities☆

Freezing point depression osmometry is preferred over vapor pressure with ingestions of volatile substances. Sixty-six laboratories nationwide (23 teaching hospital, 22 nonteaching hospital, and 21 commercial facilities) were surveyed to determine the availability and use of these techniques. Overall, 80% conducted serum osmometry (teaching, 100%; nonteaching, 82%; commercial, 57%). Freezing point depression was the most common method used by all laboratories; however, 33% of commercial laboratories and 11% of nonteaching laboratories used vapor pressure exclusively. One half of all laboratory supervisors did not identify why one method was preferred. Only 3% identified vapor pressure as a possible source of error in ingestions of volatile substances. Most laboratories estimated that they were aware of the patient diagnosis less than 50% of the time. Because vapor pressure osmometry is a potential source of false negative results when estimating serum concentrations of volatile substances, clinicians treating patients who have ingested ethanol, ethylene glycol, isopropanol, or methanol need to be aware of the methodology used in their reference laboratories.

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.