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Biomedical subjects

M J Smilkstein

Publications and source records attributed to M J Smilkstein.

At least 19 recordsLinked to original sources
PubMed1996

A pharmacokinetic comparison of acetaminophen products (Tylenol Extended Relief vs regular Tylenol)

OBJECTIVE: To compare the pharmacokinetics of Tylenol Extended Relief (ER APAP) with those of immediate-release acetaminophen (IR APAP) at supratherapeutic doses. METHODS: A prospective, double-blind, randomized, crossover comparison trial involving 14 adult volunteers. Each subject ingested 75 mg/kg of either ER APAP or IR APAP and 1 week later received the other APAP preparation. On both occasions plasma APAP concentration ([APAP]) was determined 0.5, 1, 2, 3, 4, 6, 8, 12, and 16 hours after ingestion. The times to maximum [APAP] (Tmax); the maximum [APAP] values (Cmax); the elimination half-lives 4-16 hours postingestion (t1/2), and the areas under the [APAP] vs time curve (AUC) for ER APAP and IR APAP were compared using the paired t-test. RESULTS: All the subjects completed both study phases. The mean APAP dose ingested was 5.6 g (range 4.2-7.8 g). Both the AUC and the Cmax were less after ER APAP than after IR APAP; otherwise, there was no evident difference in any measure. Graphically, ER APAP yielded a flatter, plateau-shaped curve initially, but after 4 hours the curve was nearly identical to that for IR APAP. Results are summarized in the table: [table: see text] CONCLUSION: In this model involving a single supratherapeutic dose, ER APAP evidenced no pharmacokinetic features that would suggest the need for an alternate poisoning screening strategy. When compared with IR APAP, ER APAP had a lower AUC, all peak [APAP] occurred in < 4 hours, and terminal eliminations were identical. The data suggest that, in most cases, the diagnostic approach to an overdose of ER APAP need not deviate from that used for an IR APAP overdose.

Acetaminophen↗
PubMed1994

Acetaminophen. Concepts and controversies.

APAP poisoning is common, and despite the availability of a specific antidote, fatalities still occur. Early treatment using NAC is highly effective in preventing liver injury, but further study is needed to determine optimum indications, route of administration, dosage, and duration of treatment. Recent advances have changed traditional concepts regarding late treatment and mechanisms of NAC action, but significant gaps in understanding persist. Immediate challenges include refining the diagnosis and treatment of APAP toxicity after repeated ingestions, defining settings in which deviation from standard protocols is appropriate, and improving therapy of APAP-induced hepatic failure.

Acetaminophen↗
PubMed1993

Osmol gaps revisited: normal values and limitations.

A study was designed to define the osmol gap in patients whose serum ethanol concentrations are known, to reevaluate several accepted equations for calculating osmolarity, and to apply the results to the theoretical clinical scenario of a toxic alcohol ingestion. The design for the study used consecutive, prospective enrollment of all patients presenting to a large inner city hospital who clinically required determination of their serum ethanol and electrolytes. Three hundred and twenty one consecutive adult patients were enrolled in the study, sixteen were excluded from the final analysis. A stepwise multiple linear regression analysis was performed to determine the best coefficients for sodium, blood urea nitrogen, and ethanol from the data set. Osmolarity was then calculated using these coefficients and traditional models. The osmol gap (measured osmolality minus calculated osmolarity [2*Na + BUN/2.8 + Glu/18 + Etoh/4.6]) was -2 +/- 6 mOsm. Although different equations produced different osmol gaps (ranging from -5 to + 15 mOsm) the standard deviations and correlation coefficients were similar. Large variations exist in the range of osmol gaps. Absolute values are very dependent on the equations used to calculate osmolarity. Because of the larger range of values, small osmol gaps should not be used to eliminate the possibility of toxic alcohol ingestion.

Adolescent↗
PubMed1991

Acetaminophen overdose: a 48-hour intravenous N-acetylcysteine treatment protocol.

STUDY OBJECTIVE: To determine the safety and efficacy of a 48-hour IV N-acetylcysteine (IV NAC) treatment protocol for acute acetaminophen overdose. DESIGN: Nonrandomized trial open to all eligible patients. SETTING: Multicenter; hospitals included moderate- and high-volume private, university, and municipal hospitals in urban and suburban settings. TYPE OF PARTICIPANTS: Two hundred twenty-three patients were entered. Of these, 179 met inclusion criteria: acute acetaminophen overdose, plasma acetaminophen concentration above the treatment nomogram line, treatment with IV NAC according to the protocol, and sufficient data to determine outcome. INTERVENTIONS: IV NAC treatment consisted of a loading dose of 140 mg/kg followed by 12 doses of 70 mg/kg every four hours. MEASUREMENTS AND MAIN RESULTS: Patients were grouped for analysis according to risk group based on the initial plasma acetaminophen concentration. Hepatotoxicity (aspartate aminotransferase or alanine aminotransferase of more than 1,000 IU/L) developed in 10% (five of 50) of patients at "probable risk" when IV NAC was started within ten hours of acetaminophen ingestion and in 27.1% (23 of 85) when therapy was begun after ten to 24 hours. Among "high-risk" patients first treated 16 to 24 hours after overdose, hepatotoxicity occurred in 57.9% (11 of 19). There were two deaths (two of 179, 1.1%). Adverse reactions resulting from NAC occurred in 32 of 223 cases (14.3%), consisting in 29 of 32 patients (91% of reactions) of transient, patchy, skin erythema or mild urticaria during the loading dose that did not require discontinuation of therapy. CONCLUSION: This 48-hour IV NAC protocol is safe and effective antidotal therapy for acetaminophen overdose. Based on available data, it is equal to 72-hour oral and 20-hour IV treatment protocols when started early and superior to the 20-hour IV regimen when treatment is delayed. Further study will be required to determine its relative efficacy in the high-risk patient treated very late.

Acetaminophen↗
PubMed1990

Whole bowel irrigation and the cocaine body-packer: a new approach to a common problem.

Gastrointestinal drug smuggling is a common problem in many major cities. Though the majority of cases never require medical attention, the "body-packer" frequently presents with life-threatening symptoms of intoxication, including seizures and cardiorespiratory collapse, as well as mechanical obstruction from the ingested drug packets. The risk to asymptomatic smugglers may vary with packaging materials, and remains unknown. Lack of controlled studies, and variations in packaging materials and clinical outcomes have prevented formulation of a consistent management strategy. Current recommendations for asymptomatic body-packers vary from immediate surgical removal, to use of laxatives, to observation. The authors present the first reported case of an asymptomatic cocaine body-packer treated with whole bowel irrigation with polyethylene glycol electrolyte lavage solution. This strategy was safe, well tolerated, resulted in the rapid elimination of drug packets from the gastrointestinal tract, and facilitated assessment by contrast radiography. The potential benefits and limitations for the use of whole bowel irrigation in this difficult problem are discussed.

Adult↗
PubMed1988

Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985)

During the investigational use of oral N-acetylcysteine as an antidote for poisoning with acetaminophen, 11,195 cases of suspected acetaminophen overdose were reported. We describe the outcomes of 2540 patients with acetaminophen ingestions treated with a loading dose of 140 mg of oral N-acetylcysteine per kilogram of body weight, followed four hours later by 70 mg per kilogram given every four hours for an additional 17 doses. Patients were categorized for analysis on the basis of initial plasma acetaminophen concentrations and the interval between ingestion and treatment. Hepatotoxicity developed in 6.1 percent of patients at probable risk when N-acetylcysteine was started within 10 hours of acetaminophen ingestion and in 26.4 percent of such patients when therapy was begun 10 to 24 hours after ingestion. Among patients at high risk who were treated 16 to 24 hours after an acetaminophen overdose, hepatotoxicity developed in 41 percent--a rate lower than that among historical controls. When given within eight hours of acetaminophen ingestion, N-acetylcysteine was protective regardless of the initial plasma acetaminophen concentration. There was no difference in outcome whether N-acetylcysteine was started zero to four or four to eight hours after ingestion, but efficacy decreased with further delay. There were 11 deaths among the 2540 patients (0.43 percent); in the nine fatal cases in which aminotransferase was measured before treatment, values were elevated before N-acetylcysteine was started. No deaths were clearly caused by acetaminophen among patients in whom N-acetylcysteine therapy was begun within 16 hours. We conclude that N-acetylcysteine treatment should be started within eight hours of an acetaminophen overdose, but that treatment is still indicated at least as late as 24 hours after ingestion. On the basis of available data, the 72-hour regimen of oral N-acetylcysteine is as effective as the 20-hour intravenous regimen described previously, and it may be superior when treatment is delayed.

Acetaminophen↗
PubMed1988

Magnesium levels after magnesium-containing cathartics.

To determine the effect on serum Mg++ levels of oral Magnesium-containing cathartics (MgCC) used in the treatment of suspected drug overdose, a prospective, non-randomized study of 24 cases of suspected drug overdose was conducted. Ten cases admitted to the observation unit were assigned to the single dose MgCC group. Fourteen cases admitted to either the ICU or the observation unit were assigned to the multiple dose MgCC group. Single dose cases received 30 gm of magnesium sulfate (MgSO4) at 0 hours. Multiple dose cases received 3 30 gm doses of MgSO4 at 0, 4, and 8 hours. Mg++ levels were measured prior to each MgSO4 dose and 1 and 4 hours after the final dose in both groups. In the single dose group, there was no difference between baseline Mg++ levels and post MgSO4 levels, and only 2/10 developed slightly elevated levels (2.2, 2.3 mEq/L). In the multiple dose group, levels increased and remained significantly higher than baseline after the second MgSO4 dose, and 9/14 developed elevated levels (2.2 to 5.0 mEq/L). All patients who developed elevated Mg++ levels had normal BUN and creatinine values. When the single and multiple dose groups were compared, baseline Mg++ levels were no different (1.68 +/- 0.21 vs 1.69 +/- 0.24, p = 0.952), but peak Mg++ levels were significantly higher in the multiple dose group (1.80 +/- 0.31 vs 2.61 +/- 0.86, p = 0.004). Cases that developed hypermagnesemia had slightly higher baseline Mg++ levels (1.78 +/- 0.22 vs 1.60 +/- 0.19 mEq/L, p = 0.041). In the multiple dose group, higher peak Mg++ levels were noted in cases involving ingestions of anticholinergic or opioid drugs (2.83 vs 1.98, p = 0.025). Hypermagnesemia developed in some cases with normal renal function, blood pressure, and urine output. We conclude that significant hypermagnesemia can occur rapidly after use of multiple dose Mg++ cathartics in standard doses in patients with normal renal function.

Administration, Oral↗
PubMed1988

Evaluation of coagulation factor abnormalities in long-acting anticoagulant overdose.

Newer Rodenticides of the long-acting anticoagulant or "superwarfarin" class are gaining popularity. Since few cases of severe, prolonged anticoagulation after ingestion have been reported, the course of toxicity is not precisely understood. In this case of an intentional ingestion of brodifacoum, a longitudinal analysis of specific coagulation factor derangements was carried out in an attempt to guide a future treatment strategy for this type of toxicity. Results of this analysis demonstrated a profound decrease in levels of factors II, VII, IX, and X, lasting at least 43 days post ingestion. Treatment with subcutaneous vitamin K1 in doses up to 100 milligrams per day was without complication and was effective in reversing the coagulopathy produced by brodifacoum.

4-Hydroxycoumarins↗
PubMed1987

Acute toxic blindness: unrecognized quinine poisoning.

Two cases of acute blindness due to quinine poisoning are presented. In both cases, the diagnosis was initially unsuspected. In addition, tinnitus, decreased hearing, vomiting, abdominal pain, and confusion were noted in one patient, and the other experienced decreased hearing, headache, confusion, tachycardia, later bradycardia, and first-degree atrioventricular block. The onset of blindness was delayed more than 12 hours after ingestion in both cases. Quinine levels of 13.6 micrograms/mL and 18.6 micrograms/mL were demonstrated (therapeutic = 1 to 3 micrograms/mL). One patient developed marked constriction of visual fields and some residual decreased acuity, while the other regained normal visual acuity.

Acute Disease↗