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.     

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.     

Refining the level for anticipated hepatotoxicity in acetaminophen poisoning

Treatment of an acetaminophen overdose with N-acetyl cysteine usually is based on the position of the 4-h acetaminophen (APAP) level on the Rumack-Matthew nomogram; however, there is disagreement on the level at which clinically relevant hepatotoxicity occurs. A retrospective review of all acute adult formulation APAP exposures reported to our poison center between 1986 and 1993 was performed and cases corresponding to the “possible risk or toxicity” range on the nomogram were identified. Our current poison center protocol for APAP poisoning does not recommend treatment with N-acetylcysteine (NAC) in low-risk patients if the 4-h serum APAP level or the extrapolated equivalent falls within the possible toxicity range on the nomogram. Seventeen cases met the inclusion criteria for the study and received no NAC; six additional patients met inclusion criteria but received one or two doses of NAC before therapy was discontinued. No patients in either group demonstrated clinical evidence of hepatotoxicity. This pilot study suggests that patients with no risk factors and APAP levels in the “possible risk” range may not require NAC therapy.     

Hepatotoxicity Despite Early Administration of Intravenous N-Acetylcysteine for Acute Acetaminophen Overdose

Objectives:  The objective was to evaluate the effectiveness of intravenous N -acetylcysteine (IV NAC; 300 mg/kg over 21 hours) in early acute acetaminophen (APAP) overdose patients.
Methods:  This observational case series included patients hospitalized between 2004 and 2007 for acute APAP overdoses and who were reported to a regional poison center. Inclusion criteria were plasma APAP concentrations on or above the treatment line on the Rumack-Matthew nomogram, administration of IV NAC within 8 hours of ingestion, and follow-up to known outcome. The hospital chart of each patient who received IV NAC for longer than the standard 21 hours was reviewed. Hepatotoxicity was defined as hepatic aminotransferase levels greater than 1,000 IU/L.
Results:  Seventy-seven patients met inclusion criteria and received at least 21 hours of IV NAC for an acute APAP overdose. Seven patients received antidotal therapy for greater than 21 hours. These patients tended to have ingested combination preparations, have very high initial plasma APAP concentrations, and had persistently elevated plasma concentrations during their hospital stay. Hepatotoxicity occurred in 4 patients (5.2%, 95% confidence interval [CI] = 0.2% to 10.1%), including 1 death and 1 liver transplantation.
Conclusions:  Hepatotoxicity developed in 5.2% of cases, suggesting that the 21-hour IV NAC regimen is suboptimal in some patients. In addition to high initial plasma APAP concentrations, APAP product formulation and persistently elevated plasma APAP concentrations were identified as factors possibly associated with developing hepatotoxicity. The authors propose a tailored approach to the discontinuation of IV NAC and point out the need for reevaluation of optimal doses and duration of therapy.     

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.     

Position Paper: Single-Dose Activated Charcoal

Single-dose activated charcoal therapy involves the oral administration or instillation by nasogastric tube of an aqueous preparation of activated charcoal after the ingestion of a poison. Volunteer studies demonstrate that the effectiveness of activated charcoal decreases with time. Data using at least 50 g of activated charcoal, showed a mean reduction in absorption of 47.3%, 40.07%, 16.5% and 21.13%, when activated charcoal was administered at 30 minutes, 60 minutes, 120 minutes and 180 minutes, respectively, after dosing. There are no satisfactorily designed clinical studies assessing benefit from single-dose activated charcoal to guide the use of this therapy.

Single-dose activated charcoal should not be administered routinely in the management of poisoned patients. Based on volunteer studies, the administration of activated charcoal may be considered if a patient has ingested a potentially toxic amount of a poison (which is known to be adsorbed to charcoal) up to one hour previously. Although volunteer studies demonstrate that the reduction of drug absorption decreases to values of questionable clinical importance when charcoal is administered at times greater than one hour, the potential for benefit after one hour cannot be excluded. There is no evidence that the administration of activated charcoal improves clinical outcome. Unless a patient has an intact or protected airway, the administration of charcoal is contraindicated. A review of the literature since the preparation of the 1997 Single-dose Activated Charcoal Position Statement revealed no new evidence that would require a revision of the conclusions of the Statement.     

Position paper: Single-dose activated charcoal

Single-dose activated charcoal therapy involves the oral administration or instillation by nasogastric tube of an aqueous preparation of activated charcoal after the ingestion of a poison. Volunteer studies demonstrate that the effectiveness of activated charcoal decreases with time. Data using at least 50 g of activated charcoal, showed a mean reduction in absorption of 47.3%, 40.07%, 16.5% and 21.13%, when activated charcoal was administered at 30 minutes, 60 minutes, 120 minutes and 180 minutes, respectively, after dosing. There are no satisfactorily designed clinical studies assessing benefit from single-dose activated charcoal to guide the use of this therapy. Single-dose activated charcoal should not be administered routinely in the management of poisoned patients. Based on volunteer studies, the administration of activated charcoal may be considered if a patient has ingested a potentially toxic amount of a poison (which is known to be adsorbed to charcoal) up to one hour previously. Although volunteer studies demonstrate that the reduction of drug absorption decreases to values of questionable clinical importance when charcoal is administered at times greater than one hour, the potential for benefit after one hour cannot be excluded. There is no evidence that the administration of activated charcoal improves clinical outcome. Unless a patient has an intact or protected airway, the administration of charcoal is contraindicated. A review of the literature since the preparation of the 1997 Single-dose Activated Charcoal Position Statement revealed no new evidence that would require a revision of the conclusions of the Statement.     

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.     

Prehospital gastrointestinal decontamination of toxic ingestions: A missed opportunity

The purpose of this study was to determine if emergency medical services (EMS) providers routinely initiate field gastrointestinal decontamination of adult drug overdose patients transported to the emergency department (ED). A retrospective prehospital chart review was performed on adult patients identified as drug overdose who were transported by EMS. ED charts on patients transported to a university hospital were reviewed for follow-up data. Prehospital care records showed that gastrointestinal decontamination was initiated in only 6 of 361 (2%) patients, all of whom received ipecac. No patient received activated charcoal. The median transport time was 25 minutes (range, 5 to 66 minutes). Follow-up data on patients transported to the university hospital revealed that 30 of 43 (70%) patients who might have been suitable candidates for prehospital activated charcoal actually received activated charcoal in the ED. Median time to activated charcoal in the ED was 82 minutes (range, 32 to 329 min). Use of activated charcoal in the field appears to be deferred despite its known loss of efficacy over time. The failure to start activated charcoal in the field contributes to the delay in initiating activated charcoal therapy.     

Unexpected late rise in plasma acetaminophen concentrations with change in risk stratification in acute acetaminophen overdoses

Background

The acetaminophen risk analysis nomogram is used to predict hepatotoxicity risk in acute acetaminophen overdose based on a single plasma acetaminophen concentration (PAC) measured between 4 and 24 h after ingestion. There are case reports of patients with acute overdoses of acetaminophen combination products in whom a toxic PAC occurred later after an initial non-toxic PAC at approximately 4 h.

Objectives

The objective was to describe patients who had an initial non-toxic PAC and a subsequent toxic PAC.

Methods

A poison center’s database was searched for records in which patients were administered N-acetylcysteine. Cases were included if they involved an acute overdose of an acetaminophen-containing product with at least 2 plottable PACs, the first of which was obtained at least 4 h after ingestion and was below the treatment line on the nomogram with a subsequent toxic PAC. Data were analyzed for doses, timed PACs, specific acetaminophen preparation, coingestants, activated charcoal administration, and clinical effects.

Results

Twenty patients were included. Thirteen patients ingested combination products. All patients experienced vomiting, neurologic, or cardiovascular effects at presentation or before obtaining the second PAC. Two patients developed hepatotoxicity, one of which died from the complications of acetaminophen-induced hepatotoxicity.

Conclusion

The nomogram fails to predict toxicity based on a single PAC in a small subset of patients.     

Advantage of High-surface-area Charcoal for Gastrointestinal Decontamination in a Human Acetaminophen Ingestion Model

Objective : To compare the abilities of low-surface-area (LSA) vs 2 types of high-surface-area (HSA) activated charcoal given orally to adsorb acetaminophen in the gastrointestinal (GI) tract, as demonstrated by the impact of these agents on the serum levels and area under the curve (AUC) in a simulated human overdose model. Methods : The main arm of the study was a prospective double-blind crossover trial in which 6 volunteers, serving as their own controls, ingested acetaminophen (50 mg/kg), followed randomly in 10 minutes by either powdered LSA charcoal (950 m²/g) or powdered HSA charcoal (2,000 m²/g) in a charcoal:drug ratio of 8:1. In a second arm of the study, 3 subjects additionally ingested an equal dose of a granular preparation of the HSA charcoal. Serial serum acetaminophen levels were analyzed at various intervals (30, 60, 90, 120, 180, 240, and 300 minutes postingestion), and a 5-hour AUC was calculated. The subjects also rated the charcoal preparations for palatability. Results : Serum acetaminophen levels were lower at all measured times in the groups receiving both forms of the HSA charcoal vs the LSA product. With the powdered HSA charcoal, comparison serum levels were significantly lower at 120 minutes postingestion and all times thereafter (p < 0.05), reaching high significance at 4 and 5 hours (p < 0.001). The subjects receiving the granular HSA charcoal also had consistently lower serum acetaminophen levels than did those receiving the LSA product, and the difference in mean serum levels was significant at the 4- and 5-hour sample (p = 0.012). Compared with the LSA charcoal, at the 4-hour postingestion sample, serum acetaminophen levels were reduced by 44% to 85% by the powdered HSA charcoal. The total AUC for the 5-hour study period was also significantly reduced by the powdered HSA product (p = 0.005) and the granular HSA product (p = 0.043). All the subjects rated the powdered HSA charcoal to be more palatable and easier to drink than the powdered LSA charcoal. Conclusion : The surface area of oral activated charcoal is a major determining factor in its ability to limit acetaminophen absorption and to fulfill its adsorptive role in GI decontamination. In a human acetaminophen overdose model, 2 types of HSA charcoal, when compared with equal doses of LSA charcoal, significantly reduced serum levels and total acetaminophen absorption as measured by the AUC.     

Activated charcoal: the untold story

Introduction. To identify the prevalence and appropriateness of prescribing activated charcoal in the management of acute poisoning and to document patient compliance with treatment.Methods. A prospective study was conducted, between October 1998 and September 1999, on patients attending our accident and emergency department, with a history of overdose. Overdoses were classified as potentially toxic or non-toxic according to the history and/or information received from the National Poisons Information Service.Results. Two hundred and seventy five patients presented following overdose; 17% within one hour, 102 were prescribed charcoal (37.1%) but of these, 40 (39%) refused it, and of the 62 patients (61%) who accepted charcoal only 15 (24.2%) took all that was prescribed. Patients were 5.4 times more likely to take charcoal if they had taken a potentially toxic overdose. Of those who presented within one hour and were judged to have taken a potentially toxic overdose, only three patients took the full-prescribed amount.Conclusion. We report a substantially greater proportion of patients (39%) refusing charcoal than previously reported (9.9%). The widespread availability of TOXBASE Copyright should help redress this discrepancy.     

A patient-tailored N-acetylcysteine protocol for acute acetaminophen intoxication

BACKGROUND: Hepatotoxicity as a result of acetaminophen(APAP) intoxication has become an important problem, but early intervention with N-acetylcysteine (NAC) is effective in preventing hepatic injury. Two NAC regimens are currently approved for acute APAP intoxication: NAC administered orally every 4 hours for 72 hours, and NAC administered intravenously for 20 hours within 8 to 10 hours after ingestion of a potentially hepatotoxic amount of APAP. However, clinical observations suggest that a variable treatment duration may be more appropriate than use of these predetermined, fixed-duration protocols. OBJECTIVES: This study investigated the tolerability and efficacy of a patient-tailored NAC protocol for acute APAP intoxication by comparing the incidence of hepatotoxicity in patients receiving this protocol and in historical controls receiving 1 of 2 fixed-duration protocols: oral NAC for 72 hours and intravenous NAC for 20 hours within 8 to 10 hours after ingestion of a potentially hepatotoxic amount of APAP. METHODS: This was a retrospective case series study that included all patients admitted through the emergency department (ED) of the National Taiwan University Hospital with a diagnosis of APAP intoxication between October 1997 and October 2002. According to the patient-tailored protocol, which had been used in the ED since 1997, patients with a serum APAP concentration above the limit for possible risk based on a modified Rumack-Matthew nomogram received oral treatment with NAC 140 mg/kg, followed by maintenance doses of 70 mg/kg every 4 hours. NAC treatment was discontinued when the APAP concentration was <10 mg/L and serum aspartate aminotransferase (AST) was <40 IU/L. For the purposes of assessing clinical outcomes, patients were divided into 3 groups based on duration of treatment: the short-course group (/=73 hours). The primary outcome measure was development of hepatotoxicity, defined as a serum AST or alanine aminotransferase concentration >1000 IU/L. RESULTS: Twenty-seven patients were included in the study, 17 in the short-course group, 4 in the intermediate-course group, and 6 in the long-course group. The mean (SD) durations of NAC treatment in the respective groups were 22.1 (5.5) hours, 45.0 (8.2) hours, and 97.3 (33.2) hours. All 6 patients (22%) in the long-course group had hepatotoxicity (peak AST range, 1083-9770 IU/L); their treatment duration ranged from 80 to 164 hours. No patients in the short- or intermediate-course group had evidence of hepatotoxicity. One woman in the long-course group in whom initiation of NAC treatment was delayed by 28 hours died of fulminant hepatic failure. The overall incidence of hepatotoxicity was similar to that in the historical controls. CONCLUSIONS: In this retrospective case series inpatients who received patient-tailored NAC therapy for acute APAP intoxication, the incidence of hepatotoxicity was low and comparable to that in historical controls who received treatment with 1 of 2 fixed-duration regimens. Use of this protocol may have the potential to shorten hospital stays without increasing the risk to patients. However, the sample size was small, and the findings require confirmation in prospective clinical trials.     

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.     

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.     

Poor tolerance of oral activated charcoal with theophylline overdose

Vomiting is a common manifestation of theophylline toxicity and may limit the tolerance of orally administered activated charcoal (OAC). However, this potentially important interaction has received little attention. The records of 33 consecutive patients who presented to the emergency department with serum theophylline concentrations greater than 30 micrograms/ml and toxic symptoms and who were treated with OAC were reviewed. Seventeen (22%) of the 76 OAC doses were vomited. Six patients who had ingested theophylline as a single acute overdose vomited all 11 OAC doses administered, whereas 27 patients receiving chronic theophylline therapy vomited only six (11%) of 65 OAC doses. Vomited doses were associated with higher serum theophylline concentrations. Although theophylline-related vomiting preceded OAC intolerance in all acute toxicity patients, this condition was not predictive of OAC vomiting for chronic toxicity patients.     

Activated charcoal in theophylline intoxication

To test the hypothesis that orally administered activated charcoal alters the elimination kinetics of intravenously administered theophylline, six dogs were twice infused with theophylline, 28 mg/kg, over 20 minutes 1 week apart. In a random sequence separated by 1 week, they received either activated charcoal, 30 gm in a water suspension or water only through a nasogastric tube every 2 hours after theophylline infusion, for a total of four doses. The time needed for plasma levels to fall below 20 mg/L was approximately 5 hours regardless of charcoal treatment. However, activated charcoal decreased theophylline halflife from 4.02 to 2.76 hours and volume of distribution from 0.72 to 0.61 L/kg. We conclude that although activated charcoal hastened the elimination of theophylline in dogs, the usefulness of orally administered activated charcoal in the treatment of theophylline overdose may be limited by the inability to shorten the time during which plasma levels are toxic.     

Correlation of initial amitriptyline concentration reduction with activated charcoal therapy in overdose patients

Plasma amitriptyline concentrations were measured serially in nine overdose patients and correlated with the timing and amount of each patient's initial activated charcoal therapy. A direct correlation was found between the time to initial charcoal therapy (Tc) and the plasma concentration half-life of amitriptyline (T 1/2) calculated for the first seven to 18 hours of hospitalization; T 1/2 = 2.68 + 0.047 Tc (r = 0.78, P less than 0.05). An inverse trend of T 1/2 with the initial amount of charcoal administered was also noted. Nortriptyline, the major metabolite of amitriptyline, decreased in two of three patients who received greater than or equal to 50 gm of activated charcoal within 60 minutes of presentation. These findings support previous in vitro and human volunteer studies advocating the rapid administration of activated charcoal in acute tricyclic antidepressant overdoses.     

N-乙酰半胱氨酸在慢性阻塞性肺疾病急性加重患者的疗效观察

目的:观察N-乙酰半胱氨酸(NAC)在治疗急性加重期慢性阻塞性肺疾病患者(AECOPD)的疗效及耐受性。方法:122例AECOPD患者随机分成二组,除常规治疗外,治疗组加用NAC600μg/天,对照组不用NAC,治疗15天后观察C反应蛋白(CRP)正常率、血气分析、症状改善、肺功能及耐受性。结果:CRP正常率两组均比治疗前明显升高,治疗后治疗组比对照组CRP正常率也明显增高(86·7%vs65·5%,P<0·05);PaO2及PaCO2变化:组内比较:治疗组及对照组均比治疗前PaO2明显升高(P<0·05),PaCO2明显下降(P<0·05)。组间比较:治疗后PaO2治疗组比对照组明显升高(P<0·05),PaCO2未见显著差异(P>0·05);临床症状改善:治疗组比对照组总有效率明显升高(90%vs74·1%P<0·05),临床症状改善明显;肺功能:治疗组FEV1及FVC均比治疗前明显改善(P<0·05),而对照组治疗前后无显著差异(P>0·05);治疗过程中二组耐受性均良好,未见较为严重的不良反应。结论:口服NAC600μg/天治疗可以明显改善AECOPD的CRP水平和临床症状,改善氧饱和度及肺功能,耐受性好。     

Acetaminophen poisoning: an evidence-based consensus guideline for out-of-hospital management

The objective of this guideline is to assist poison center personnel in the appropriate out-of-hospital triage and initial management of patients with suspected ingestions of acetaminophen. An evidence-based expert consensus process was used to create this guideline. This guideline applies to ingestion of acetaminophen alone and is based on an assessment of current scientific and clinical information. The expert consensus panel recognizes that specific patient care decisions may be at variance with this guideline and are the prerogative of the patient and the health professionals providing care. The panel's recommendations follow. These recommendations are provided in chronological order of likely clinical use. The grade of recommendation is provided in parentheses. 1) The initial history obtained by the specialist in poison information should include the patient's age and intent (Grade B), the specific formulation and dose of acetaminophen, the ingestion pattern (single or multiple), duration of ingestion (Grade B), and concomitant medications that might have been ingested (Grade D). 2) Any patient with stated or suspected self-harm or who is the recipient of a potentially malicious administration of acetaminophen should be referred to an emergency department immediately regardless of the amount ingested. This referral should be guided by local poison center procedures (Grade D). 3) Activated charcoal can be considered if local poison center policies support its prehospital use, a toxic dose of acetaminophen has been taken, and fewer than 2 hours have elapsed since the ingestion (Grade A). Gastrointestinal decontamination could be particularly important if acetylcysteine cannot be administered within 8 hours of ingestion. Acute, single, unintentional ingestion of acetaminophen: 1) Any patient with signs consistent with acetaminophen poisoning (e.g., repeated vomiting, abdominal tenderness in the right upper quadrant or mental status changes) should be referred to an emergency department for evaluation (Grade D). 2) Patients less than 6 years of age should be referred to an emergency department if the estimated acute ingestion amount is unknown or is 200 mg/kg or more. Patients can be observed at home if the dose ingested is less than 200 mg/kg (Grade B). 3) Patients 6 years of age or older should be referred to an emergency department if they have ingested at least 10 g or 200 mg/kg (whichever is lower) or when the amount ingested is unknown (Grade D). 4) Patients referred to an emergency department should arrive in time to have a stat serum acetaminophen concentration determined at 4 hours after ingestion or as soon as possible thereafter. If the time of ingestion is unknown, the patient should be referred to an emergency department immediately (Grade D). 5) If the initial contact with the poison center occurs more than 36 hours after the ingestion and the patient is well, the patient does not require further evaluation for acetaminophen toxicity (Grade D). Repeated supratherapeutic ingestion of acetaminophen (RSTI): 1) Patients under 6 years of age should be referred to an emergency department immediately if they have ingested: a) 200 mg/kg or more over a single 24-hour period, or b) 150 mg/kg or more per 24-hour period for the preceding 48 hours, or c) 100 mg/kg or more per 24-hour period for the preceding 72 hours or longer (Grade C). 2) Patients 6 years of age or older should be referred to an emergency department if they have ingested: a) at least 10 g or 200 mg/kg (whichever is less) over a single 24-hour period, or b) at least 6 g or 150 mg/kg (whichever is less) per 24-hour period for the preceding 48 hours or longer. In patients with conditions purported to increase susceptibility to acetaminophen toxicity (alcoholism, isoniazid use, prolonged fasting), the dose of acetaminophen considered as RSTI should be greater than 4 g or 100 mg/kg (whichever is less) per day (Grade D). 3) Gastrointestinal decontamination is not needed (Grade D). Other recommendations: 1) The out-of-hospital management of extended-release acetaminophen or multi-drug combination products containing acetaminophen is the same as an ingestion of acetaminophen alone (Grade D). However, the effects of other drugs might require referral to an emergency department in accordance with the poison center's normal triage criteria. 2) The use of cimetidine as an antidote is not recommended (Grade A).