Methods Used to Decrease Lithium Absorption or Enhance Elimination

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.     

Successful Use of Hemodialysis in Acute Valproic Acid Intoxication

Background: Increased clearance and apparent clinical improvement in valproic acid overdose has been reported following in-series hemodialysis/hemoperfusion therapy. We report a case of divalproex sodium and chlorpheniramine overdose treated with charcoal hemoperfusion and multiple-dose activated charcoal. Case Report: A 32-year-old female presented alert three hours postingestion of her own medication. Serum valproic acid was 105 μg/mL. No anticholinergic toxicity was seen. Despite three doses of activated charcoal over 14 hours, serum valproic acid continued to rise. Whole bowel irrigation and multiple-dose activated charcoal were commenced 17?h postingestion when serum valproic acid was 1380 μg/mL. Charcoal hemoperfusion was instituted three hours later when serum valproic acid had not fallen and the patient remained obtunded. Results: Initial extraction ratio of the hemoperfusion cartridge was 0.54 with plasma clearance of 54.5 mL/min. Valproic acid elimination half-life was 3?h during the 190 min hemoperfusion cycle. Posthemoperfusion elimination half-life was 4.8?h with continued multiple-dose activated charcoal dosing. The clinical condition improved during hemoperfusion. Conclusion: Enteric coated valproic acid preparations may cause delayed toxicity in overdose, particularly with coingested anticholinergic medications. In our case, charcoal hemoperfusion appeared to increase valproic acid clearance.     

Effect of Magnesium Hydroxide on Iron Absorption Following Simulated Mild Iron Overdose in Human Subjects

Abstract. Objective:To determine the effect of oral magnesium hydroxide [Mg(OH)₂] on iron absorption after simulated iron overdose in human subjects.
Methods:A randomized, controlled crossover study was conducted in healthy adult male human volunteers taking no medications. Subjects received an average of 5.0 mg/kg elemental iron orally followed 1 hour later by either oral administration of 4.5 g of Mg(OH)₂ per g ingested elemental iron or no treatment. Serial serum specimens were obtained over the 12 hours following iron ingestion and stored at -60^oC until standard serum iron assay was performed. After a 2-week washout period, the subjects were enrolled in the alternative trial arm. Individual baseline diurnal variation in serum iron levels was determined over a 12-hour period on the day prior to each trial. Area under time-concentration curves (AUCs) were calculated, and the AUC due to experimental iron ingestion (ΔAUC) was determined by subtracting the baseline diurnal AUC from the experimental AUC for each subject.
Results:Thirteen healthy adult male subjects were enrolled. Mean ± SEM for ΔAUC due to experimental iron ingestion followed by treatment with Mg(OH)₂, 78 ± 23 |xmol(hr)/L, was significantly less than that followed by no treatment, 144 ± 33 p.mol(hr)/L (p = 0.03 by signed rank test).
Conclusions:Magnesium hydroxide, administered 1 hour post-iron ingestion at an oral dose of 4.5 g per g elemental iron ingested, significantly reduced iron absorption during a 12-hour period following simulated mild iron overdose in healthy adult human volunteers.     

Efficacy of superactivated charcoal administered late (3 hours) after acetaminophen overdose

The purpose of this study was to investigate the effect of superactivated charcoal (SAC) given late after a drug overdose. Acetaminophen was chosen as our overdose drug because it has relatively few side effects, serum levels are easily attainable and measurable, and it is generally a common drug overdose. Forty-six healthy adult volunteers participated in this randomized, controlled study. Acetaminophen was administered the morning after an overnight fast. Thirteen participants received 2000 mg acetaminophen and the remaining 33 received 3000 mg. After 3 hours, half of the participants (22 of 46) received 75 g of SAC (Requa, Greenwich, CT) orally as a slurry in 8 oz of apple juice. Serum acetaminophen levels were measured at 4 and 7 hours after the initial acetaminophen administration. There were significantly lower uncorrected and corrected acetaminophen levels in the SAC group compared with the control group at both 4 and 7 hours after ingesting acetaminophen. This randomized human experimental design trial demonstrates some detoxification benefit in administering superactivated charcoal 3 hours after an overdose.     

Nomogram line crossing after acetaminophen combination product overdose

Background: The Rumack–Matthew nomogram predicts the risk of hepatotoxicity following acute acetaminophen overdose based on a serum concentration obtained?≥4-hour post-ingestion. Some patients with low-risk concentrations at 4 hours may have subsequent values indicating increased risk (above the nomogram treatment line), especially if coingestants that slow gastrointestinal motility are involved. The treatment line currently used to identify low risk patients in the United States, Canada, and Australia begins at 150?mcg/mL (993?μmol/L) and intersects at 18.75?mcg/mL (124.1?μmol/L) 16 hours post-ingestion. Objective: To determine the incidence of nomogram line crossing after acute overdose of acetaminophen combination products containing an opioid or antihistamine. Methods: This was a prospective cohort study of hospitalized patients reported to a regional poison center (RPC) after acute overdose of a combination product containing an opioid or antihistamine. If a 4-hour acetaminophen concentration was detectable but below the nomogram treatment line, the RPC recommended repeat concentrations. Patients were entered into the study if at least one subsequent concentration was available. During follow-up calls hospital providers were queried regarding clinical features, treatment, and indicators of liver injury. Results: Over a 4-year period 76 patients met entry criteria. 5/76 (6.6%) had measureable acetaminophen concentrations below the treatment line at or close to 4-hour post-ingestion followed by values above the line obtained at 6.5–12.5 hours. Four of the five were treated with acetylcysteine and none developed hepatotoxicity. Four of the five had clinical features reported to the RPC suggesting toxicity from the opioid or antihistamine component. Conclusion: After acute overdose of acetaminophen combination products, patients with detectable but non-toxic 4-hour acetaminophen concentrations should have repeat concentrations obtained in a time frame that would allow providers to initiate acetylcysteine treatment, if needed, without undue delay.     

Activated Charcoal Reduces the Need for N-Acetylcysteine Treatment After Acetaminophen (Paracetamol) Overdose

Background: The evidence for efficacy of gastric lavage and activated charcoal for gastrointestinal decontamination in poisoning has relied entirely on volunteer studies and/or pharmacokinetic studies and evidence for any clinical benefits or resource savings is lacking. au1,Aim of Study: To investigate the value of gastrointestinal decontamination using gastric lavage and/or activated charcoal in acetaminophen (paracetamol) poisoning. Patients and Methods: We analyzed a series of 981 consecutive acetaminophen poisonings. These patients were treated with gastric lavage and activated charcoal, activated charcoal alone, or no gastrointestinal decontamination. The decision as to which treatment was received was determined by patient cooperation, the treating physician, coinigested drugs, and time to presentation after the overdose. Results: Of 981 patients admitted over 10 years, 10% (100) had serum concentrations of acetaminophen that indicated a probable or high risk of hepatotoxicity. The risk of toxic concentrations for patients ingesting less than 10 g of acetaminophen was very low. In patients presenting within 24 hours, who had ingested 10 g or more, those who had been given activated charcoal were significantly less likely to have probable or high risk concentrations (Odds ratio 0.36, 95% CI 0.23–0.58, p < 0.0001). Gastric lavage, in addition to activated charcoal, did not further decrease the risk (Odds ratio 1.12, 95% CI 0.57–2.20, p = 0.86). Conclusions: Toxic concentrations of serum acetaminophen (paracetamol) are uncommon in patients ingesting less than 10 g. In those ingesting more, activated charcoal appears to reduce the number of patients who achieve toxic acetaminophen concentrations and thus may reduce the need for treatment and hospital stay.     

Massive overdose with controlled‐release carbamazepine resulting in delayed peak serum concentrations and life‐threatening toxicity

Introduction: Peak serum levels following overdose with immediate‐release formulations of carbamazepine have been reported to occur up to 2 days postingestion. We report a case of poisoning with carbamazepine controlled‐release resulting in peak levels 96 h postingestion. Case Reports: A 31‐year‐old female presented following a suspected polypharmacy overdose. She was haemodynamically stable with a Glasgow Coma Scale score of 3 and was endotracheally intubated in the emergency department. A single‐dose of activated charcoal was administered on admission and her neurological status improved gradually. Results of qualitative urine drug screen available 24 h postadmission to the intensive care department revealed benzodiazepines and carbamazepine. The serum carbamazepine concentration at this time was 66 µmol/L (therapeutic 17–42 µmol/L). A history of therapy with controlled‐release carbamazepine was discovered. Repeat‐dose activated charcoal and whole‐bowel irrigation were commenced, but poorly tolerated. Serum carbamazepine levels continued to rise and gastrointestinal tract decontamination was ceased due to the presence of an ileus. By day 4, the serum carbamazepine concentration peaked at 196 µmol/L. This was associated with coma, generalized intermittent seizure activity and hypotension. Charcoal haemoperfusion was commenced due the presence of end‐organ toxicity and failed gastrointestinal tract decontamination. Serum carbamazepine concentrations fell from 176 to 106 µmol/L after 1 h of haemoperfusion and the patient was rousable to voice and could obey commands at this time. She confirmed ingestion of 300 Tegretol‐CR® (200 mg) on extubation and was discharged without long‐term sequelae. Conclusion: Unrecognized poisoning with controlled‐release carbamazepine has the potential to produce significant delayed carbamazepine toxicity and delayed peak serum carbamazepine concentrations. This may occur much later than previously reported with immediate‐release carbamazepine preparations.     

Effect of Anticholinergic Drugs on the Efficacy of Activated Charcoal

Background: Although it is a commonly held belief that the ingestion of drugs with an anticholinergic action would prolong the duration of time after drug ingestion for effective gastrointestinal decontamination, data are lacking to support this belief. The purpose of this study is to determine whether activated charcoal is more effective in the presence of concurrent anticholinergic activity. Methods: A three‐limbed randomized crossover study in 10 healthy volunteers was completed to determine the ability of a 50 g dose of activated charcoal to reduce the bioavailability of a simulated overdose of acetaminophen (12 × 325 mg tablets) in the presence and absence of a concurrently present anticholinergic drug, atropine (0.01 mg/kg I. M. administered 15 min prior to the acetaminophen ingestion). Results: After the acetaminophen ingestion, median C_max occurred at 1 h for all three exposures but was lower in the atropine‐treated study arm (31 ± 19 mg/L) than in the control or charcoal alone intervention arms (49 ± 13 and 51 ± 16 mg/L, respectively) (P < 0.05). Compared to the control area under the serum concentration vs. time curve, a single dose of activated charcoal 1 h after drug ingestion reduced acetaminophen bioavailability by 20% (95% CI 4–36%) and by 47% (95% CI 35–59%) in the presence of atropine (P < 0.05 atropine plus charcoal vs. charcoal alone). Conclusions: Our data support the belief that activated charcoal is more effective in the presence of anticholinergic activity. Additional study is required to determine whether in patients with anticholinergic drug overdose, activated charcoal is effective at times beyond the recommendation for overdoses of drugs without this pharmacodynamic effect.     

A Pharmacokinetic Comparison of Acetaminophen Products (Tylenol Extended Relief vs Regular Tylenol)

Obiedive: 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 mgkg 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] (T_max); the maximum [APAP] values (C_max); the elimination half-lives 4–16 hours postingestion (t_1/2), 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 C_max 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:

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.     

Efficacy of activated charcoal administered more than four hours after acetaminophen overdose

To evaluate whether administration of activated charcoal, in addition to standard N-acetylcysteine (NAC) therapy, after acetaminophen overdose provides additional patient benefit over NAC therapy alone, a 1-year non-randomized prospective, multi-center, observational case series was performed at three poison centers and one poison center system. Entrance criteria were all acute acetaminophen overdoses with: 1) an acetaminophen blood concentration determined to be in the toxic range by the Rumack-Matthew nomogram; and 2) all therapies, including NAC and activated charcoal, initiated between 4 and 16 h post-ingestion. There were 145 patients meeting entrance criteria, of whom 58 patients (40%) received NAC only and 87 patients (60%) received NAC and activated charcoal. Overall, 23 patients had elevations of AST or ALT greater than 1000 IU/L, of which 21 patients received NAC only (38% of total NAC only group) and 2 patients received NAC and activated charcoal (2% of total NAC+AC group). Administration of activated charcoal in this series of patients with toxic acetaminophen concentrations treated with NAC was associated with reduced incidence of liver injury, as measured by elevated serum transaminases and prothrombin times.     

Impact of activated charcoal after acute acetaminophen overdoses treated with N-acetylcysteine

Previous studies have suggested that patients receiving both activated charcoal (AC) and N-acetylcysteine (NAC) after acute acetaminophen (APAP) overdoses may have improved outcomes. We evaluated all acute acetaminophen overdoses that received NAC therapy reported to US poison centers for the years 1993 through 2004. Groups were separated based on therapy received: 1) both AC and NAC and 2) NAC alone. There were 97,960 acetaminophen overdoses reported, with 49,427 patients (50%) receiving NAC and AC. Reports of AST/ALT > 1000, a major effect, and death were 1301 (2.9%), 2957 (6.6%), and 232 (0.5%), respectively, for patients receiving NAC plus AC, vs. 5273 (12%), 4534 (10.3%), and 369 (0.8%), respectively, for patients receiving NAC alone (p < 0.01). Use of Toxic Exposure Surveillance System data in the present study has a number of limitations, including its retrospective nature and no documentation of when NAC therapy was initiated. It is possible that those patients who did not receive AC presented to the Emergency Department later in their overdose and had NAC therapy initiated later, and therefore they were predisposed to a greater risk of hepatic injury. Evaluation of 12 years of acute APAP overdoses suggests that the use of AC, in addition to NAC therapy, may provide improved patient outcomes.     

Diltiazem overdose: case report and review

We present a case of diltiazem overdose in which the patient ingested 4.2 grams in an apparent suicide attempt. He arrived in the emergency department two hours postingestion with a blood pressure of 60/40 torr and a heart rate of 62 beats/min in a junctional rhythm. Intervention included activated charcoal, gastric lavage, intravenous fluids, calcium (both chloride and gluconate), dopamine, and atropine with improvement in vital signs. Diltiazem levels were obtained and half-life calculated. This ingestion is one of the largest reported in the literature and is remarkable in that the patient recovered without pacing or other extraordinary measures. All eight previously published cases of diltiazem overdose, including all unpublished reports to the manufacturer, are reviewed and their management strategies examined. Successful treatment in which recovery has occurred in less than 48 hours, includes pressors, calcium, glucagon, pacing, and charcoal hemoperfusion. A strategy for emergency physicians to use when approaching this problem is suggested from the review.     

The Use of Cholecystokinin as an Adjunctive Treatment for Toxin Ingestion

Study Objective: To determine if pharmacologic trapping of ingested toxins in the stomach using cholecystokinin (CCK) in addition to activated charcoal (AC) decreases the absorption of ingested toxins. Methods: We performed a two‐phase study that was prospective, randomized, blinded, and placebo‐controlled, using a subtoxic acetaminophen (APAP) animal model. Eight adult beagle dogs were studied to detect a 20% decrease in 4h APAP levels with a power of 80%. A control arm using APAP at 100 mg/kg without AC or CCK was first performed. APAP levels were drawn at 0.5, 1, 1.5, 2, 4, 8, and 24h. This was repeated in a CCK dose finding phase using a 60‐min CCK infusion (4 vs. 8 pmol/kg/min) starting at 30 min post‐APAP ingestion. Once the optimal CCK dose was established, animals in the treatment phase received AC and a 1h infusion of CCK (vs. placebo). The efficacy of CCK when started at 30 and 60 min post‐APAP ingestion was tested. Results: In the dose finding arm 8 pmol/kg/min was well tolerated and also reduced maximum APAP levels by a mean of 49% from control. This dose was then used for the treatment phase. Four‐hour APAP levels, maximum APAP levels, and area under the curve (AUC) were measured. No significant differences were found between placebo and CCK arms at either the 30 or 60 min postingestion interventions. Conclusions: In this model, CCK infusion did not decrease the absorption of APAP. Adding charcoal to the model overcame the suggested beneficial effect of CCK alone in the dosing arm.     

The effect of yogurt on acetaminophen absorption by activated charcoal and burnt toast

Although acetaminophen overdose can be treated with N-acetylcysteine, activated charcoal is useful in preventing absorption of acetaminophen from the gut. Mixing activated charcoal with yogurt may make the dose more palatable. We investigated effects of yogurt on absorption of acetaminophen by burnt toast or activated charcoal in intestinal fluid using an in vitro model. The aliquots of phosphate buffer saline (PBS) were supplemented with high concentrations of acetaminophen after adjusting the pH to 7.2 (to mimic intestinal fluid). Then specimens were treated with various dosages (15 mg/mL, 25 mg/mL, or 50 mg/mL) of activated charcoal or burnt toast. A small amount of fluid was withdrawn at 0, 5, 10, 20, and 30 min and acetaminophen concentrations were measured by the fluorescence polarization immunoassay (FPIA). We also treated other aliquots of PBS buffer containing acetaminophen with activated charcoal and yogurt or burnt toast and yogurt. Then small aliquots were withdrawn at specific time intervals to determine concentrations of acetaminophen. Activated charcoal was very effective in removing acetaminophen from intestinal fluids and the presence of yogurt insignificantly affected such absorptions. In contrast, burnt toast had a modest effect on removing acetaminophen from fluids but yogurt significantly increased the capability of burnt toast to absorb acetaminophen. However, the activated charcoal/yogurt combination is more effective than the burnt toast/yogurt combination for absorbing acetaminophen.     

The effect of nateglinide taken with food on gastric emptying rates in healthy subjects

OBJECTIVES: The aim of this study was to determine the effect of the timing of food intake on the pharmacokinetics and pharmacodynamics of oral nateglinide 60 mg and the effect of nateglinide on the rate of gastric emptying. METHODS: A randomized, double-blind, placebo-controlled, single-dose, 6-period, crossover study conducted in healthy male volunteers aged 18 to 50 years. On 5 occasions, subjects received a single 60-mg tablet of nateglinide at -30, -10, -5, -1, or 40 minutes from the start of a standard metal. Treatment blind was maintained by administration of placebo tablets at all other time points. On the sixth occasion, subjects received placebo tablets at all dosing time points. Each subject received acetaminophen 1 g at the beginning of the standard breakfast on each treatment day as an indicator of the rate of gastric emptying. Plasma samples were collected over a 6-hour period to determine nateglinide, glucose, insulin, and acetaminophen concentrations. RESULTS: Twelve white men with a mean (SD) age of 30 (6.8) years (range, 21-47 years) and mean (SD) weight of 73.3 (11.0) kg completed all 6 periods of the study. Nateglinide absorption was faster when administered at -5 or -10 minutes relative to food, as characterized by higher nateglinide area under the concentration-time curve from 0 to 5 hours (AUC(0-5)) and maximum plasma concentration (C(max)) values, compared with those observed at other dosing time points. Mean time to C(max) (T(max)) was also shorter when nateglinide was given at -10 minutes versus other dosing time points. Mean nateglinide half-life was similar for all 5 treatments (range, 81.3-94.6 minutes). The overall treatment effect was statistically significant for nateglinide AUC(0-5) (P = 0.031), C(max) (P = 0.001), and T(max) (P < 0.001). Insulin T(max) was shorter after nateglinide administration at -30 or -10 minutes, which was associated with lower glucose C(max) values (-30 minutes, P < 0.05) and a tendency for lower glucose AUC(0-5) values (-10 minutes, P = NS). NS). No treatment effects were observed for any of the acetaminophen indices, as demonstrated by the absence of any change in acetaminophen T(max) or C(max) value. CONCLUSIONS: Nateglinide was well tolerated and no treatment-limiting adverse events were reported in the population studied. Nateglinide administration appeared to have no effect on the rate of gastric emptying as indicated by acetaminophen indices, regardless of the time of nateglinide administration. The findings imply that the time for nateglinide administration to obtain optimal pharmacodynamic effects is prior to food consumption.     

Acupressure for Prevention of Emesis in Patients Receiving Activated Charcoal

Objective: Vomiting after activated charcoal decontamination is problematic. Acupressure (traditional Chinese medicine) is an effective treatment for emesis, but has not been tested in overdose patients. We sought to determine (1) the incidence of emesis after activated charcoal and (2) the ability of acupressure to prevent emesis due to activated charcoal. Methods: Consecutive overdose patients were enrolled in a preliminary, prospective study to determine the incidence of emesis after activated charcoal. Awake patients, >18 years, received 1 g/kg activated charcoal orally or via nasogastric tube, and then observed for 1 hour. These patients served as controls for part 2 of the study, where acupressure bands were placed on overdose patients at the Nei-Guan P-6 point of both wrists prior to activated charcoal, followed by 1 hour observation. Exclusion criteria included: ipecac decontamination, antiemetic drug ingestion, antiemetic drug therapy within 1 hour of activated charcoal, or intubation. Results: Eighty-one patients were included in the control group and 106 patients in the acupressure treatment group. Demographics and ingested substances were similar in both groups. 21/81 (25.9%) in the control group vomited and 15/106 (14.2%) in the acupressure group vomited. Acupressure reduced emesis by 46% (p=0.043; χ²). Within the acupressure group, the median duration of prophylactic acupressure was 5 minutes in those patients without vomiting compared to 4 minutes in those patients with vomiting (NS; Wilcoxon rank sum test). Conclusion: The incidence of emesis after activated charcoal at our institution was 26%. Prophylactic acupressure reduced activated charcoal-induced vomiting by 46%. Investigators suggest 5 minutes of acupressure prior to activated charcoal.     

Are recommended doses of acetaminophen hepatotoxic for recently abstinent alcoholics? A randomized trial

Although acetaminophen overdose is a leading cause of fulminant hepatic failure, it is controversial whether therapeutic doses of acetaminophen can cause hepatotoxicity in alcoholics, especially those rendered most vulnerable by recent abstinence. We performed a randomized, triple-blind, parallel-group trial comparing sustained-release acetaminophen, 1300 mg orally q8h for 11 doses, against placebo. We enrolled chronic alcohol abusers (defined as >or= 6 drinks daily for >or= 6 weeks) who had discontinued alcohol consumption 12 to 72 hours prior to enrollment. Individuals with self-reported viral hepatitis, HIV or intravenous drug use, baseline AST or ALT >120 IU/L, or INR >1.5 were excluded. Hepatic function tests were drawn daily for 5 days. The primary outcome was change in serum alpha-GST, a sensitive experimental biomarker of hepatocellular injury; secondary outcomes were changes in serum AST, ALT, INR, and study withdrawal for a doubling of aminotransferases to >120 IU/L. Of 52 subjects randomized, 40 completed at least four days of intervention. Subjects receiving acetaminophen had 32% [95% CI 7%, 50%] and 29% [6%, 46%] lower serum alpha-GST concentrations on days 2 and 3, respectively, compared to placebo, but these differences disappeared by day 4. No subjects were withdrawn for safety reasons. In conclusion, therapeutic doses of sustained-release acetaminophen cause a measurable decrease in serum alpha-GST during the first days of abstinence from chronic alcohol use. While the mechanism is unclear, these observations do provide some reassurance that short courses of acetaminophen are unlikely to cause subclinical hepatocellular injury in recently abstinent alcoholics.     

Predictive Properties of a Qualitative Urine Acetaminophen Screen in Patients with Self-Poisoning

Objective: Screening for acetaminophen toxicity is recommended in almost all cases of self poisoning. We compared a qualitative urine acetaminophen screen to the quantitative serum acetaminophen to test the hypothesis that a negative urine acetaminophen screen would be predictive of a negative serum acetaminophen level. Methods: All adults with intentional ingestions evaluated in our Emergency Department during 1995 were retrospectively identified based on Emergency Department International Classification of Disease–9th edition codes. Laboratory data from each patient including serum and urine toxicologic assays were examined. Predictive properties of urine acetaminophen screens for serum acetaminophen were evaluated.Results: A total of 88 patients were identified who had both a serum acetaminophen and a urine acetaminophen performed. The sensitivity of the urine acetaminophen screen was 100% (95% CI 72–100%) and the specificity was 87% (95% CI 80–95%). All patients with negative urine acetaminophen screens had negative serum acetaminophen levels (negative predictive value 100%; 95% CI 96–100%). Accuracy of the urine acetaminophen screen was 89%. Conclusion: A negative urine acetaminophen screen was highly predictive of negative serum acetaminophen levels. It is possible that negative urine acetaminophen screens may obviate the need for 4-hour quantitative serum levels. Further validation in a prospective study is needed.     

Whole-bowel irrigation versus activated charcoal in sorbitol for the ingestion of modified-release pharmaceuticals

Overdose with modified-release pharmaceuticals is an increasing phenomenon. This study examines whole-bowel irrigation as a potential decontamination strategy after overdose with enteric-coated acetylsalicylic acid and compares it with administration of activated charcoal in sorbitol, which is currently the recommended intervention. A three-phase randomized crossover protocol was used in 10 adult volunteers. Each volunteer ingested nine 325 mg doses of enteric-coated acetylsalicylic acid on three occasions, with at least 1 week between each administration period. Serum samples were analyzed for salicylic acid concentration by HPLC. Both interventions decreased peak salicylic acid concentration, time-to-zero salicylic acid concentration, and AUC when compared with control (p less than 0.01). Whole-bowel irrigation was superior to activated charcoal in sorbitol by all three criteria (p less than 0.05). Adverse effects were qualitatively and quantitatively greater during activated charcoal in sorbitol, and the volunteers preferred whole-bowel irrigation over charcoal in sorbitol. Our data suggest that whole-bowel irrigation should be considered for overdose of other modified-release pharmaceuticals.     

The effect of activated charcoal on N-acetylcysteine absorption in normal subjects

The discovery of the effectiveness of oral antidotes such as N-acetylcysteine (NAC) for acetaminophen poisonings has raised questions about the appropriateness of concomitant administration with activated charcoal. A number of studies have attempted to clarify this question without complete success. This study was designed to evaluate the difference in serum levels of NAC when given with activated charcoal. Nineteen patients completed a two-phase cross-over study in which they served as their own controls. Each subject in phase 1 received 140 mg/kg of diluted, chilled NAC orally, and venous blood samples were drawn for analysis. Phase 2 consisted of a 100-g dose of activated charcoal followed by NAC. Samples were transported immediately and assayed using spectrophotometry. A reduction in peak NAC level of 29% (P less than .02) and a reduction of total area under the curve (AUC) of 39% (P less than .001) was noted. Although it may be preferable to avoid completely the use of activated charcoal when using NAC to treat overdoses of acetaminophen, we recommend that if these agents are used together, doses of NAC be increased by 40% to compensate for the decreased oral absorption of NAC.