Nonsteroidal antiinflammatory drug (NSAID) poisoning
- Mark Su, MD, MPH
Mark Su, MD, MPH
- Clinical Associate Professor of Emergency Medicine
- New York University School of Medicine
- Arun Nagdev, MD
Arun Nagdev, MD
- Medicine Director, Emergency Ultrasound
- Highland General Hospital
- Assistant Clinical Professor
- University of California, San Francisco
Millions of people worldwide take nonsteroidal antiinflammatory drugs (NSAIDs) on a regular basis to treat pain and inflammation. Patients with an acute overdose of NSAIDs often present to emergency departments and represent a sizable percentage of cases reported to regional poison centers . As aging populations have increasingly come to rely on NSAIDs, chronic toxicity and acute poisonings have become more commonplace. Given the relative frequency of toxic NSAID exposures, emergency and primary care clinicians need to understand the diagnosis and management of this poisoning.
Acute NSAID poisoning is reviewed here. A summary table to facilitate emergent management is provided (table 1). A general approach to suspected drug intoxication and discussions of chronic NSAID toxicity are provided elsewhere. (See "General approach to drug poisoning in adults" and "Nonselective NSAIDs: Overview of adverse effects".)
NSAIDs are competitive inhibitors of the enzyme cyclooxygenase (COX) (figure 1). NSAIDs prevent COX-mediated production of prostaglandins and thromboxanes but not leukotrienes and other eicosanoids. (See "NSAIDs: Mechanism of action".)
There are two COX isoforms, COX-1 and COX-2. The constitutive enzyme, COX-1, is expressed in most tissues and enables regulation of basal cellular homeostasis (platelet function, gastric mucosal integrity, and regulation of renal blood flow). The activity of the inducible COX-2 isoenzyme increases in inflammatory and pain states .
Numerous animal and human studies have demonstrated the role of COX-1 in inflammation [3,4]. In general, all NSAIDs inhibit both isoforms, with most adverse reactions believed to be attributable to COX-1 inhibition. The development of newer COX-2 selective NSAIDs arose from the desire to maintain therapeutic antiinflammatory function, while decreasing the rates of adverse drug effects, most notably gastrointestinal and renal toxicity. (See "Nonselective NSAIDs: Overview of adverse effects".)
- Bronstein AC, Spyker DA, Cantilena LR Jr, et al. 2008 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 26th Annual Report. Clin Toxicol (Phila) 2009; 47:911.
- Parente L, Perretti M. Advances in the pathophysiology of constitutive and inducible cyclooxygenases: two enzymes in the spotlight. Biochem Pharmacol 2003; 65:153.
- Wallace JL, Bak A, McKnight W, et al. Cyclooxygenase 1 contributes to inflammatory responses in rats and mice: implications for gastrointestinal toxicity. Gastroenterology 1998; 115:101.
- Ochi T, Goto T. Differential effect of FR122047, a selective cyclo-oxygenase-1 inhibitor, in rat chronic models of arthritis. Br J Pharmacol 2002; 135:782.
- Goldfrank LR, Flomenbaum NE, Lewin NA, et al. Goldfrank's Toxicologic Emergencies, 7th, McGraw-Hill, New York 2002.
- Smolinske SC, Hall AH, Vandenberg SA, et al. Toxic effects of nonsteroidal anti-inflammatory drugs in overdose. An overview of recent evidence on clinical effects and dose-response relationships. Drug Saf 1990; 5:252.
- Volans G, Monaghan J, Colbridge M. Ibuprofen overdose. Int J Clin Pract Suppl 2003; :54.
- Holubek W, Stolbach A, Nurok S, et al. A report of two deaths from massive ibuprofen ingestion. J Med Toxicol 2007; 3:52.
- Desai PR, Sriskandan S. Hypothermia in a child secondary to ibuprofen. Arch Dis Child 2003; 88:87.
- Wood DM, Monaghan J, Streete P, et al. Fatality after deliberate ingestion of sustained-release ibuprofen: a case report. Crit Care 2006; 10:R44.
- Marciniak KE, Thomas IH, Brogan TV, et al. Massive ibuprofen overdose requiring extracorporeal membrane oxygenation for cardiovascular support. Pediatr Crit Care Med 2007; 8:180.
- Levine M, Khurana A, Ruha AM. Polyuria, acidosis, and coma following massive ibuprofen ingestion. J Med Toxicol 2010; 6:315.
- Gambaro G, Perazella MA. Adverse renal effects of anti-inflammatory agents: evaluation of selective and nonselective cyclooxygenase inhibitors. J Intern Med 2003; 253:643.
- Griffin MR, Yared A, Ray WA. Nonsteroidal antiinflammatory drugs and acute renal failure in elderly persons. Am J Epidemiol 2000; 151:488.
- Whelton A, Schulman G, Wallemark C, et al. Effects of celecoxib and naproxen on renal function in the elderly. Arch Intern Med 2000; 160:1465.
- Whelton A. Renal and related cardiovascular effects of conventional and COX-2-specific NSAIDs and non-NSAID analgesics. Am J Ther 2000; 7:63.
- Murray MD, Brater DC. Renal toxicity of the nonsteroidal anti-inflammatory drugs. Annu Rev Pharmacol Toxicol 1993; 33:435.
- McElwee NE, Veltri JC, Bradford DC, Rollins DE. A prospective, population-based study of acute ibuprofen overdose: complications are rare and routine serum levels not warranted. Ann Emerg Med 1990; 19:657.
- Vale JA, Meredith TJ. Acute poisoning due to non-steroidal anti-inflammatory drugs. Clinical features and management. Med Toxicol 1986; 1:12.
- Robson RH, Balali M, Critchley J, et al. Mefenamic acid poisoning and epilepsy. Br Med J 1979; 2:1438.
- Balali-Mood M, Critchley JA, Proudfoot AT, Prescott LF. Mefenamic acid overdosage. Lancet 1981; 1:1354.
- Kingswell RS. Mefenamic acid overdose. Lancet 1981; 2:307.
- Steinhauer HB, Hertting G. Lowering of the convulsive threshold by non-steroidal anti-inflammatory drugs. Eur J Pharmacol 1981; 69:199.
- Frank JJ, Wightkin WT, Hubner JW. Acute toxicity of nonsteroidal antiinflammatory agents: seizure following a mefenamic acid overdose. Drug Intell Clin Pharm 1983; 17:204.
- Sánchez-Hernandez MC, Delgado J, Navarro AM, et al. Seizures induced by NSAID. Allergy 1999; 54:90.
- Risks of agranulocytosis and aplastic anemia. A first report of their relation to drug use with special reference to analgesics. The International Agranulocytosis and Aplastic Anemia Study. JAMA 1986; 256:1749.
- Nelson L, Shih R, Hoffman R. Aplastic anemia induced by an adulterated herbal medication. J Toxicol Clin Toxicol 1995; 33:467.
- Hall AH, Smolinske SC, Stover B, et al. Ibuprofen overdose in adults. J Toxicol Clin Toxicol 1992; 30:23.
- Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol 1999; 37:731.
- Court H, Volans GN. Poisoning after overdose with non-steroidal anti-inflammatory drugs. Adverse Drug React Acute Poisoning Rev 1984; 3:1.
- Martinez R, Smith DW, Frankel LR. Severe metabolic acidosis after acute naproxen sodium ingestion. Ann Emerg Med 1989; 18:1102.
- Le HT, Bosse GM, Tsai Y. Ibuprofen overdose complicated by renal failure, adult respiratory distress syndrome, and metabolic acidosis. J Toxicol Clin Toxicol 1994; 32:315.
- Seifert SA, Bronstein AC, McGuire T. Massive ibuprofen ingestion with survival. J Toxicol Clin Toxicol 2000; 38:55.
- Oker EE, Hermann L, Baum CR, et al. Serious toxicity in a young child due to ibuprofen. Acad Emerg Med 2000; 7:821.
- Zuckerman GB, Uy CC. Shock, metabolic acidosis, and coma following ibuprofen overdose in a child. Ann Pharmacother 1995; 29:869.
- Downie A, Ali A, Bell D. Severe metabolic acidosis complicating massive ibuprofen overdose. Postgrad Med J 1993; 69:575.
- Hall AH, Smolinske SC, Kulig KW, Rumack BH. Ibuprofen overdose--a prospective study. West J Med 1988; 148:653.
- Lee CY, Finkler A. Acute intoxication due to ibuprofen overdose. Arch Pathol Lab Med 1986; 110:747.
- Hall AH, Smolinske SC, Conrad FL, et al. Ibuprofen overdose: 126 cases. Ann Emerg Med 1986; 15:1308.
- Court H, Streete P, Volans GN. Acute poisoning with ibuprofen. Hum Toxicol 1983; 2:381.
- Virji MA, Venkataraman ST, Lower DR, Rao KN. Role of laboratory in the management of phenylbutazone poisoning. J Toxicol Clin Toxicol 2003; 41:1013.
- HISTORY AND PHYSICAL EXAMINATION
- CLINICAL ASPECTS OF ACUTE TOXICITY
- Acid base abnormalities
- Acute renal failure
- Cardiovascular toxicity
- Central nervous system toxicity
- Hematological toxicity
- Allergic reactions
- LABORATORY EVALUATION
- General diagnostic testing
- Testing for NSAID toxicity
- DIFFERENTIAL DIAGNOSIS
- MANAGEMENT OF ACUTE TOXICITY
- Airway, breathing, circulation
- Gastrointestinal decontamination
- Other supportive measures
- Extracorporeal removal
- Patient disposition
- CHRONIC TOXICITY
- ADDITIONAL RESOURCES
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS