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Biomedical subjects

N A Buckley

Publications and source records attributed to N A Buckley.

At least 19 recordsLinked to original sources
PubMed2006

Antidotes for acute cardenolide (cardiac glycoside) poisoning.

BACKGROUND: Cardenolides are naturally occurring plant toxins which act primarily on the heart. While poisoning with the digitalis cardenolides (digoxin and digitoxin) are reported worldwide, cardiotoxicity from other cardenolides such as the yellow oleander are also a major problem, with tens of thousands of cases of poisoning each year in South Asia. Because cardenolides from these plants are structurally similar, acute poisonings are managed using similar treatments. The benefit of these treatments is of interest, particularly in the context of cost since most poisonings occur in developing countries where resources are very limited. OBJECTIVES: To determine the efficacy of antidotes for the treatment of acute cardenolide poisoning, in particular atropine, isoprenaline (isoproterenol), multiple-dose activated charcoal (MDAC), fructose-1,6-diphosphate, sodium bicarbonate, magnesium, phenytoin and anti-digoxin Fab antitoxin. SEARCH STRATEGY: We searched MEDLINE, EMBASE, the Controlled Trials Register of the Cochrane Collaboration, Current Awareness in Clinical Toxicology, Info Trac, www.google.com.au, and Science Citation Index of studies identified by the previous searches. We manually searched the bibliographies of identified articles and personally contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials where antidotes were administered to patients with acute symptomatic cardenolide poisoning were identified. DATA COLLECTION AND ANALYSIS: We independently extracted data on study design, including the method of randomisation, participant characteristics, type of intervention and outcomes from each study. We independently assessed methodological quality of the included studies. A pooled analysis was not appropriate. MAIN RESULTS: Two randomised controlled trials were identified, both were conducted in patients with yellow oleander poisoning. One trial investigated the effect of MDAC on mortality, the relative risk (RR) was 0.31 (95% confidence interval (CI) 0.12 to 0.83) indicating a beneficial effect. The second study found a beneficial effect of anti-digoxin Fab antitoxin on the presence of cardiac dysrhythmias at two hours post-administration; the RR was 0.60 (95% CI 0.44 to 0.81). Other benefits were also noted in both studies and serious adverse effects were minimal. Studies assessing the effect of antidotes on other cardenolides were not identified. One ongoing study investigating the activated charcoal for acute yellow oleander self-poisoning was also identified. AUTHORS' CONCLUSIONS: There is some evidence to suggest that MDAC and anti-digoxin Fab antitoxin may be effective treatments for yellow oleander poisoning. However, the efficacy and indications of these interventions for the treatment of acute digitalis poisoning is uncertain due to the lack of good quality controlled clinical trials. Given pharmacokinetic differences between individual cardenolides, the effect of antidotes administered to patients with yellow oleander poisoning cannot be readily translated to those of other cardenolides. Unfortunately cost limits the use of antidotes such as anti-digoxin Fab antitoxin in developing countries where cardenolide poisonings are frequent. More research is required using relatively cheap antidotes which may also be effective.

Acute Disease↗
PubMed2006

Respiratory failure in acute organophosphorus pesticide self-poisoning.

BACKGROUND: Acute organophosphorus (OP) pesticide poisoning is a major clinical problem in the developing world. Textbooks ascribe most deaths to respiratory failure occurring in one of two distinct clinical syndromes: acute cholinergic respiratory failure or the intermediate syndrome. Delayed failure appears to be due to respiratory muscle weakness, but its pathophysiology is unclear. AIM: To describe the clinical patterns of OP-induced respiratory failure, and to determine whether the two syndromes are clinically distinct. DESIGN: Prospective study of 376 patients with confirmed OP poisoning. METHODS: Patients were observed throughout their admission to three Sri Lankan hospitals. Exposure was confirmed by butyrylcholinesterase and blood OP assays. RESULTS: Ninety of 376 patients (24%) required intubation: 52 (58%) within 2 h of admission while unconscious with cholinergic features. Twenty-nine (32%) were well on admission but then required intubation after 24 h while conscious and without cholinergic features. These two syndromes were not clinically distinct and had much overlap. In particular, some patients who required intubation on arrival subsequently recovered consciousness but could not be extubated, requiring ventilation for up to 6 days. DISCUSSION: Respiratory failure did not occur as two discrete clinical syndromes within distinct time frames. Instead, the pattern of failure was variable and overlapped in some patients. There seemed to be two underlying mechanisms (an early acute mixed central and peripheral respiratory failure, and a late peripheral respiratory failure) rather than two distinct clinical syndromes.

Acute Disease↗
PubMed2006

Identification of strategies to prevent death after pesticide self-poisoning using a Haddon matrix.

Despite pesticide self-poisoning causing around 300 000 deaths each year in the rural Asia Pacific region, no comprehensive public health response has yet been formulated. The authors have developed a Haddon matrix to identify factors that increase the risk of fatal rather than non-fatal pesticide self-poisoning in Sri Lanka. Many important host factors such as age, gender, and genetics are not alterable; factors that could be changed-alcohol use and mental health-have previously proved difficult to change. Interventions affecting agent or environmental factors may be easier to implement and more effective, in particular those limiting the human toxicity and accessibility of the pesticides, and the quality, affordability, and accessibility of health care in the community. Controlled studies are required to identify effective strategies for prevention and harm minimization and to garner political support for making the changes necessary to reduce this waste of life. Lessons learnt from Sri Lanka are likely to be highly relevant for much of rural Asia.

Alcohol Drinking↗
PubMed2005

A randomized clinical trial of activated charcoal for the routine management of oral drug overdose.

BACKGROUND: Activated charcoal (AC) is commonly used for the routine management of oral drug overdose. AIM: To determine whether the routine use of activated charcoal has an effect on patient outcomes. DESIGN: Randomized controlled unblinded trial. METHODS: We recruited all adult patients presenting with an oral overdose at The Canberra Hospital, excluding only transfers, late presenters, those who had ingested drugs not adsorbed by activated charcoal or where administration was contraindicated, and very serious ingestions (at the discretion of the admitting physician). Patients were randomized to either activated charcoal or no decontamination. RESULTS: The trial recruited 327 patients over 16 months. Of 411 presentations, four refused consent, 27 were protocol violations and 53 were excluded from the trial. Only seven were excluded due to the severity of their ingestion. The most common substances ingested were benzodiazepines, paracetamol and selective serotonin reuptake inhibitor antidepressants. More than 80% of patients presented within 4 h following ingestion. There were no differences between AC and no decontamination in terms of length of stay (AC 6.75 h, IQR 4-14 vs. controls 5.5 h, IQR 3-12; p=0.11) or secondary outcomes including vomiting, mortality and intensive care admission. DISCUSSION: Routine administration of charcoal following oral overdose did not significantly influence length of stay or other patient outcomes following oral drug overdose. There were few adverse events. This does not exclude a role in patients who present shortly after ingestion of highly lethal drugs.

Acetaminophen↗
PubMed2005

Hyperbaric oxygen for carbon monoxide poisoning.

BACKGROUND: Poisoning with carbon monoxide (CO) remains an important cause of accidental and intentional injury worldwide. Several unblinded non-randomized trials have suggested that the use of hyperbaric oxygen (HBO) prevents the development of neurological sequelae. This has led to the widespread use of HBO in the management of patients with carbon monoxide poisoning. OBJECTIVES: To examine randomized trials of the effectiveness of hyperbaric oxygen (HBO) compared to normobaric oxygen (NBO) for the prevention of neurologic sequelae in patients with acute carbon monoxide poisoning. SEARCH STRATEGY: We searched MEDLINE (1966-present), EMBASE (1980-present), and the Controlled Trials Register of the Cochrane Collaboration, supplemented by a manual review of bibliographies of identified articles and discussion with recognized content experts. SELECTION CRITERIA: All randomized controlled trials involving non-pregnant adults acutely poisoned with carbon monoxide (regardless of severity), with adequate or unclear allocation concealment. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted from each trial information on: the number of randomized patients, types of participants, the dose and duration of the intervention, and the prevalence of neurologic symptoms at follow-up. MAIN RESULTS: Seven randomized controlled trials of varying quality were identified; one was excluded because it did not evaluate clinical outcomes. Of the six remaining trials, two represent incomplete publications (one interim analysis, one abstract). Of these six trials, four found no benefit of HBO for the reduction of neurologic sequelae, while two others did. Although pooled analysis does not suggest a benefit from HBOT (OR for neurological deficits 0.78, 95%CI 0.54 to 1.12, p=0.18), significant methodologic and statistical heterogeneity was apparent among the trials, and this result should be interpreted cautiously. Moreover, design or analysis flaws were evident in all trials. Importantly, the conclusions of one positive trial may have been influenced by failure to adjust for multiple hypothesis testing, while interpretation of the other positive trial is hampered by apparent changes in the primary outcome during the course of the trial. AUTHORS' CONCLUSIONS: Existing randomized trials do not establish whether the administration of HBO to patients with carbon monoxide poisoning reduces the incidence of adverse neurologic outcomes. Additional research is needed to better define the role, if any, of HBO in the treatment of patients with carbon monoxide poisoning. This research question is ideally suited to a multi-center randomized controlled trial.

Carbon Monoxide Poisoning↗
PubMed2005

Alkalinisation for organophosphorus pesticide poisoning.

BACKGROUND: Poisoning with organophosphorus pesticides (OPs) is an important cause of morbidity and mortality in all parts of the world, particularly developing countries. The case-fatality ratio for pesticide intentional self-poisoning is around 10-20% even when the standard antidotes (atropine, oximes and benzodiazepines) are used. Alternative treatments have been trialled in an attempt to improve outcomes from acute OP poisoning, one of which is plasma alkalinisation. Animal and preliminary human research has suggested benefit from plasma alkalinisation with sodium bicarbonate (NaHCO3) as a treatment for acute OP poisoning. OBJECTIVES: To determine the efficacy of alkalinisation, in particular NaHCO3, for the treatment of acute OP poisoning. SEARCH STRATEGY: We searched MEDLINE (1966-2004), EMBASE (1980-2004), the Controlled Trials Register of the Cochrane Collaboration, Current Awareness in Clinical Toxicology, Info Trac, http://www.google.com.au, and Science Citation Index of studies identified by the previous searches. We also manually reviewed the bibliographies of identified articles and personally contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials and controlled clinical trials of symptomatic patients following acute OP poisoning treated with alkalinisation. The quality of studies and eligibility for inclusion was assessed using criteria by Jadad and Schulz. DATA COLLECTION AND ANALYSIS: Studies were identified and both authors independently extracted data which was recorded on a pre-designed form. Study design, including the method of randomisation, participant characteristics, type of intervention and outcomes were recorded. Outcomes were discussed, but unfortunately specific analyses could not be performed, given the poor quality of the studies identified. MAIN RESULTS: Five studies were identified but none satisfied inclusion criteria. NaHCO3 was used in each of these to induce alkalinisation. Two studies were uncontrolled, two studies were historically controlled and one study was randomised but poorly concealed. Marked heterogeneity between subjects and treatments was noted - for example, a different regimen of NaHCO3 was used in each study. While there may have been a trend towards improved outcomes (lower total dose of atropine and shorter length of stay), these were not statistically significant. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the routine use of plasma alkalinisation for treatment of OP poisoning. Further research is required to determine the method of alkalinisation that will optimise outcomes, and the regimen which will produce the target arterial pH of 7.50 (range 7.45-7.55). This should be followed by a well-designed randomised controlled trial to determine efficacy.

Humans↗
PubMed2005

Oximes for acute organophosphate pesticide poisoning.

BACKGROUND: Acute organophosphorus pesticide poisoning causes tens of thousands of deaths each year across the developing world. Standard treatment involves administration of intravenous atropine and oxime to counter acetylcholinesterase inhibition at the synapse. The usefulness of oximes, such as pralidoxime and obidoxime, has been challenged over the past 20 years by physicians in many parts of the world, who have failed to see benefit in their clinical practice. OBJECTIVES: To find the clinical trial evidence for oximes producing clinical benefit in acute organophosphorus pesticide-poisoned patients. SEARCH STRATEGY: We carried out a systematic search to find randomised clinical trials (RCTs) of oximes in acute organophosphorus pesticide poisoning, using MEDLINE, EMBASE and Cochrane databases. All articles with the text words 'organophosphate' or 'oxime' together with 'poisoning' or 'overdose' were examined. (Search last updated November 2003.) SELECTION CRITERIA: Articles that could possibly be randomised clinical trials were retrieved to determine if this was the case. DATA COLLECTION AND ANALYSIS: The published methodology of the possible RCTs located is not clear. One was found in abstract form only and two other published trials also had many gaps in the published methodology. We have attempted to contact the principal authors of all three trials but have been unable to obtain further information. MAIN RESULTS: Two RCTs have been published, involving 182 patients treated with pralidoxime. These trials did not find benefit. However, the studies did not take into account a number of issues important for outcome and the methodology is unclear. Therefore, a generalised statement on effectiveness cannot be supported by the published results. In particular, characteristics at baseline were not evenly balanced, the dose of oxime was much lower than recommended in guidelines, there were substantial delays to treatment, and the type of organophosphate was not taken into account. The abstract of the third trial, a small possible RCT, is uninterpretable without further data. AUTHORS' CONCLUSIONS: Current evidence is insufficient to indicate whether oximes are harmful or beneficial in the management of acute organophosphorus pesticide poisoning. A much larger RCT is required to compare the World Health Organization recommended pralidoxime regimen (>30 mg/kg bolus followed by >8 mg/kg/hr infusion) with placebo. There are many theoretical and practical reasons why oximes may not be useful to patients with overwhelming self-poisoning. Such a study will need to be designed with pre-defined sub-group analysis to allow identification of patient sub-groups that may benefit from oximes.

Antidotes↗
PubMed2005

Experiences of anticholinesterase pesticide poisonings in an Australian tertiary hospital.

There is limited information regarding the management and outcomes of patients presenting with anticholinesterase pesticide poisoning in Australia. Patients presenting to a tertiary referral hospital with anticholinesterase exposures were identified by discharge coding. The medical records of each patient were retrospectively reviewed. Based on clinical outcome, patients were classified as severe or non-severe poisonings. Forty-one presentations were noted between 1990 and 2003. Eight patients (20%) had severe poisoning of which tachycardia, fasciculations with weakness and metabolic acidosis were common manifestations. The diagnosis was delayed in four patients due to the absence of a clear history, which did not influence patient outcomes or put hospital staff at risk of nosocomial poisoning. The median length of hospital stay was prolonged in severe poisonings (20 days) compared to 12 hours in other patients. Two cases of intermediate syndrome were attributed to fenthion and diazinon, and one case of delayed polyneuropathy to trichlorfon. Cholinesterase activities were performed in only 49% of presentations. The overall mortality was 2.4% (1 death) and the mortality in patients with severe poisoning was 12.5%. The incidence of anticholinesterase poisoning in Australia is low. These outcomes were favourable and comparable with other published data. Measures to enhance the knowledge of medical staff supplemented by validated treatment protocols should be developed. For less significant exposures, an emphasis on adequate documentation of cholinergic signs and cholinesterase activities is necessary for rapid triage and may also have potential forensic implications if not performed.

Adolescent↗
PubMed2003

Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) and venlafaxine have been regarded as less toxic in overdose than tricyclic antidepressants (TCAs). Within the TCAs, dothiepin has greater toxicity. Venlafaxine may be more toxic than SSRIs. AIM: To assess the toxicity in overdose of venlafaxine and SSRIs compared to TCAs, and of dothiepin compared to other TCAs. DESIGN: Cohort study of prospectively collected data from the Hunter area, NSW, Australia. METHODS: First admissions with antidepressant deliberate self-poisoning (DSP) (November 1994 to April 2000) were identified; the presence of seizures, life-threatening arrhythmias, coma, serotonin toxicity or ICU admission, and QRS duration were noted. RESULTS: There were 538 admissions, with no deaths. The odds ratio (OR) for seizures with dothiepin vs. other TCAs was 3.4 (95%CI 1.2-9.9). Seizures occurred in 7/51 (14%) venlafaxine overdoses; all patients with seizures consumed > or =900 mg. The OR for seizures vs. TCAs was 4.4 (95%CI 1.4-13.8). Coma was less likely with venlafaxine and SSRIs. SSRIs, but not venlafaxine, were less likely to prolong the QRS to > or =100 ms. ICU admission was less likely for SSRIs. Serotonin toxicity was much more common with venlafaxine and SSRIs. DISCUSSION: Venlafaxine and dothiepin are pro-convulsant in overdose. Venlafaxine is more likely to cause serotonin toxicity, but less likely to cause coma than TCAs. SSRIs are less likely to cause coma, require ICU admission, or prolong the QRS, but are more likely to cause serotonin toxicity. Antidepressants other than TCAs or venlafaxine should be considered in patients at risk of seizure or suicide.

Adolescent↗
PubMed2003

Prospects for treatment of paraquat-induced lung fibrosis with immunosuppressive drugs and the need for better prediction of outcome: a systematic review.

BACKGROUND: Acute paraquat self-poisoning is a significant problem in parts of Asia, the Pacific and the Caribbean. Ingestion of large amounts of paraquat results in rapid death, but smaller doses often cause a delayed lung fibrosis that is usually fatal. Anti-neutrophil ('immunosuppressive') treatment has been recommended to prevent lung fibrosis, but there is no consensus on efficacy. AIM: To review the evidence for the use of immunosuppression in paraquat poisoning, and to identify validated prognostic systems that would allow the use of data from historical control studies and the future identification of patients who might benefit from immunosuppression. DESIGN: Systematic review. METHODS: We searched PubMed, Embase and Cochrane databases for 'paraquat' together with 'poisoning' or 'overdose'. We cross-checked references and contacted experts, and searched on [www.google.com] and [www.yahoo.com] using 'paraquat', 'cyclophosphamide', 'methylprednisolone' and 'prognosis'. RESULTS: We found ten clinical studies of immunosuppression in paraquat poisoning. One was a randomized controlled trial (RCT). Seven used historical controls only; the other two were small (n = 1 and n = 4). Mortality in controls and patients varied markedly between studies. Three of the seven non-RCT controlled studies measured plasma paraquat; analysis using Proudfoot's or Hart's nomograms did not suggest that immunosuppression increased survival in these studies. Of 16 prognostic systems for paraquat poisoning, none has been independently validated in a large cohort. DISCUSSION: The authors of the RCT have performed valuable and difficult research, but their results are hypothesis-forming rather than conclusive; elsewhere, the use of historical controls is problematic. In the absence of a validated prognostic marker, a large RCT of immunosuppression using death as the primary outcome is required. This RCT should also prospectively test and validate the available prognostic methods, so that future patients can be selected for this and other therapies on admission.

Acute Disease↗
PubMed2001

Poisoning with the recreational drug paramethoxyamphetamine ("death").

OBJECTIVE: To describe the clinical features of paramethoxyamphetamine (PMA; "death") poisoning and to compare these with those of people with self-reported "ecstasy" poisoning. DESIGN: Retrospective casenote review. PARTICIPANTS AND SETTING: 22 patients who presented to the Emergency Department of the Royal Adelaide Hospital (RAH), a major metropolitan teaching hospital, between 1 January 1996 and 31 December 1998 with PMA poisoning identified through urine drug screens; and 61 patients with self-reported ecstasy poisoning between 1 September 1997 and 31 December 1998 found through the hospital databases. RESULTS: Patients with PMA poisoning presented with tachycardia (64%), hyperthermia (temperature > 37.5 degrees C; 36%), coma (41%), seizures (32%), arrhythmias (23%), and QRS intervals > or = 100 ms (50%) with greater frequency and often greater severity than those with self-reported ecstasy poisoning. Two patients with PMA poisoning presented with severe hypoglycaemia (blood glucose level, < 1.5 mmol/L) accompanied by hyperkalaemia (K+ concentration, > 7.5 mmol/L). CONCLUSIONS: At our hospital, PMA poisonings accounted for most of the severe reactions among people who believed they had taken ecstasy. Hypoglycaemia and hyperkalaemia may be specific to PMA poisoning. PMA toxicity should be suspected with severe or atypical reactions to "ecstasy", and confirmed by chromatographic urine drug screens.

Adolescent↗
PubMed2000

Acetaminophen causes an increased International Normalized Ratio by reducing functional factor VII.

Acetaminophen may increase International Normalized Ratio (INR) in patients taking anticoagulation medication, and in patients with acetaminophen poisoning without hepatic injury. The objective of this study was to describe and investigate the effect of acetaminophen on INR. The authors studied patients admitted to a regional toxicology treatment center with acetaminophen poisoning with INR and without potentially confounding coingestion or hepatic injury. Exposed and nonexposed (control) cohorts were recruited from admissions with acetaminophen poisoning and psychotropic drug poisoning, respectively. From 1,437 acetaminophen poisonings, after exclusions, there were 143 admissions with 205 estimations of INR. INR showed a time-dependent increase. Fifty percent of all patients and 66% of those with an extrapolated 4-hour acetaminophen concentration > or = 150 mg/L had an abnormal INR at some time. Dose ingested (p = 0.01) and nomogram-based risk (p for trend = 0.005) were correlated with the effect. N-acetylcysteine had a protective effect. Functional factor VII was lower (p = 0.005) in exposed patients (n = 30) than controls (n = 8), and less than antigenic factor VII in exposed patients (p = 0.03). Factor IX was lower (p = 0.02). Factor VIIIc was not significantly different. The authors concluded that an isolated, small rise in INR is common after acetaminophen poisoning without hepatic injury. It appears to be caused by inhibition of Vitamin K-dependent activation of coagulation factors. This effect suggests a possible mechanism for the observed interaction between acetaminophen and warfarin.

Acetaminophen↗
PubMed2000

Cardiovascular adverse effects of antipsychotic drugs.

Minor cardiovascular adverse effects from antipsychotic drugs are extremely common. They include effects such as postural hypotension and tachycardia due to anticholinergic or alpha1-adrenoceptor blockade, and may occur in the majority of patients at therapeutic dosages. There are a number of pharmacological effects that are of uncertain clinical significance, such as blockade of calmodulin, sodium and calcium channels and alpha2-adrenoceptors in the central nervous system. The most serious consequences of treatment, arrhythmias and sudden death, are probably uncommon and are most likely to be caused primarily by blockade of cardiac potassium channels such as HERG. Incomplete evidence suggests that arrhythmias and sudden death are a particular problem with certain drugs (thioridazine and droperidol), high risk populations (elderly, pre-existing cardiovascular disease, inherited disorders of cardiac ion channels or of antipsychotic drug metabolism) or people taking interacting drugs (such as drugs that prolong the QT interval, e.g. tricyclic antidepressants, drugs that inhibit antipsychotic drug metabolism, or diuretics). Clozapine may be unique in also causing death from myocarditis and cardiomyopathy. Much further research is required to more clearly identify high risk drugs and the populations that are at risk of sudden death, as well as the mechanisms involved and the extent of the risk.

Adult↗
PubMed1999

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. 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, coingested 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.

Acetaminophen↗
PubMed1999

Oral or intravenous N-acetylcysteine: which is the treatment of choice for acetaminophen (paracetamol) poisoning?

BACKGROUND: The optimal route and duration of administration for N-acetyl-cysteine in the management of acetaminophen (paracetamol) poisoning are controversial. It has been stated on the basis of a selected post-hoc analysis that oral N-acetylcysteine is superior to intravenous N-acetylcysteine in presentations later than 15 hours. AIM OF STUDY: To investigate the efficacy of intravenous or oral N-acetylcysteine. PATIENTS AND METHODS: We analyzed a series of acetaminophen poisonings treated with a protocol including activated charcoal and intravenous N-acetylcysteine. The outcomes assessed included use of N-acetylcysteine, adverse effects of intravenous N-acetylcysteine, and the occurrence of hepatotoxicity (transaminase > 1000 U/L). We incorporated these results in a meta-analysis of previously reported series of acetaminophen poisonings to compare the outcomes from intravenous and oral N-acetylcysteine use. RESULTS: Of 981 patients admitted over 10 years, 4% (40) presented later than 24 hours and 10% (100) had concentrations of acetaminophen that indicated a probable or high risk of hepatotoxicity. The 30 patients who developed hepatotoxicity presented later, took larger amounts, had higher concentrations, and received N-acetylcysteine later than those who did not. No patients received a liver transplant but 2 patients died (one after referral to a transplant unit and one just before). Adverse reactions to intravenous N-acetylcysteine occurred in 6% (12/205) of patients but none prevented completion of the treatment. In the meta-analysis, those with probable or high risk concentrations had similar outcomes with intravenous (pooled n = 341) and oral N-acetylcysteine (pooled n = 1462) administration. Rates of hepatotoxicity for those treated within 10 hours (3 and 6%), late (10-24 hours: 30 and 26%), and overall (0-24 hours: 16 and 19%) were all similar. The proportion of patients classified as presenting later than 10 hours is much greater in the oral N-acetylcysteine studies (64%) than in many of the intravenous N-acetylcysteine studies (38%, 44%, and 63%). CONCLUSIONS: The differences claimed between oral and intravenous N-acetylcysteine regimes are probably artifactual and relate to inappropriate subgroup analysis. A shorter hospital stay, patient and doctor convenience, and the concerns over the reduction in bioavailability of oral N-acetylcysteine by charcoal and vomiting make intravenous N-acetylcysteine preferable for most patients with acetaminophen poisoning.

Acetaminophen↗