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Drug Overdoses during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Acetaminophen levels measured at times post-ingestion can broadly predict whether or not hepatotoxicity should be expected (Figure 14.2). The Rumack-Matthews nomogram (Figure 14.2) is based in part on clinical observations made on 662 non-pregnant adults with acetaminophen overdose (Rumack et al., 1981).
Acetaminophen, Salicylates, and Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Published in Frank A. Barile, Barile’s Clinical Toxicology, 2019
Initial symptoms are nonspecific, and a careful history and an acetaminophen plasma level should be performed so that impending toxicity is not missed. This affords the patient the opportunity of early treatment and prevention of potential irreversible hepatic damage. A quiescent recovery period (Stage 2) is characterized by clinical improvement after 24 to 72 h post ingestion. Treatment at this stage is generally based on laboratory findings and acetaminophen plasma levels. Liver function tests are monitored throughout the critical periods until complete recovery is ensured. It is important to note that the acetaminophen plasma levels based on the Rumack–Matthew nomogram are intended for single acute overdose and do not apply in suspected toxicity with chronic or prolonged ingestion of therapeutic doses. Monitoring these patients involves the same criteria as noted in Table 18.1, especially the determination of drug concentrations every 2 to 4 h to establish baseline toxicity criteria. Continued observation and repeat levels are warranted.
Acute pain management in the intensive care unit
Published in Pamela E Macintyre, Suellen M Walker, David J Rowbotham, Clinical Pain Management, 2008
Paracetamol is a centrally acting analgesic used to treat mild to moderate pain and pyrexia.118 Severe hepatotoxicity can occur when standard doses are given to patients with liver dysfunction.119 The Rumack–Matthew nomogram is not applicable to patients with chronic overdosage.120, 121
Evaluation of N-acetylcysteine dose for the treatment of massive acetaminophen ingestion
Published in Clinical Toxicology, 2022
J. C. Lewis, M. Lim, L. Lai, E. Mendoza, T. E. Albertson, J. A. Chenoweth
Acetaminophen (APAP) overdose is the most common cause of drug-induced hepatic failure in the United States [1]. N-acetylcysteine (NAC) is the standard of care for the prevention of acute liver injury after APAP overdose and treatment of hepatotoxicity after APAP poisoning [2]. NAC is known to be highly effective, especially when initiated within 8 h of an overdose [3]. The major proposed mechanism is thought to be through restoration of hepatic glutathione levels and detoxification of the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI) that is formed in excess during an overdose of APAP [3,4]. Clinical management of acute APAP ingestions utilize the Rumack-Matthew nomogram to estimate the likelihood of developing hepatotoxicity which helps clinicians determine if treatment with NAC is necessary [5]. There is currently no universal consensus on the definition of a massive APAP overdose. Based on current available literature, some have defined it as an ingestion larger than 30 g or an APAP serum concentration twice the level on the 150 mcg/mL treatment line on the Rumack-Matthew nomogram (e.g., 300 mcg/mL at 4 h) [6].
A review of alternative intravenous acetylcysteine regimens for acetaminophen overdose
Published in Expert Review of Clinical Pharmacology, 2021
Kevin Burnham, Tianrui Yang, Haleigh Smith, Steven Knight
The Rumack–Matthew nomogram, a prediction tool for hepatotoxicity after an acetaminophen overdose, was developed in the 1970s. The nomogram graph acetaminophen blood concentration against the time since ingestion. The original line was developed using a concentration-time plot of 64 patients in a poison unit. The nomogram line demarcated which patients experienced an acute elevation in serum aspartate transferase (AST) > 1000 IU during their stay in the unit. This evaluation led to the creation of the 200-line, which starts with 200 mg/L at 4 h and intersects with points following a slope that depicts a half-life of 4 h. This nomogram was slightly modified to a 150-line for use in initial FDA-approval studies, which was created lowering the 200-line by 25% [18]. This 150-line has withstood the test of time as it is still referenced by poison centers and emergency departments in most countries.
5-Oxoproline concentrations in acute acetaminophen overdose
Published in Clinical Toxicology, 2020
Michael E. Mullins, Mary S. Jones, Robert D. Nerenz, Evan S. Schwarz, Dennis J. Dietzen
We carried out an IRB-approved observational study over nine months (1 December 2013–31 August 2014). We enrolled all adults and children with measureable plasma APAP following acute APAP overdose. We aimed to include patients with APAP concentrations that were potentially toxic using the “150 line” of the Rumack–Matthew nomogram. We obtained aliquots of remaining plasma in lithium heparin (green top) tubes obtained during routine blood draws during each patient’s admission. We measured 5-oxoproline as its trimethylsilyl derivative by gas chromatography/mass spectrometry using an HP 6890 Gas Chromatograph coupled to the HP 5973 Mass Selective Detector (Agilent Technologies, Inc., Santa Clara, CA). We compared 5-oxoproline concentrations to other laboratory values including acetaminophen concentration, transaminases, anion gap, creatinine, international normalized ratio (INR), and total bilirubin. Assays for acetaminophen, electrolytes, ALT, AST, creatinine, and total bilirubin occurred using Roche Cobas/Modular Chemistry Analyzers (Roche Diagnostics, Indianapolis, IN). Prothrombin time measurement occurred using an ACL TOP analyzer (Instrumentation Labs, Bedford, MA) or a STA Compact analyzer (Diagnostica Stago, Parsipanny, NJ) with values expressed as International Normalized Ratio (INR).