New appreciation of serious adverse drug reactions

The Canadian Adverse Events Study evaluated the incidence of adverse events related to medical mismanagement in Canadian hospitals.[1] Since adverse drug reactions were included in the analysis, this important Canadian study provides information to help prevent serious adverse drug reactions from occurring in our country. What changes can we make based on this information?

In this study, 3745 charts from 20 hospitals across Canada were reviewed retrospectively for serious adverse events, defined as those resulting in death, disability, or prolonged hospital stay, that arose from medical mismanagement in the year 2000. Serious adverse events were detected in 255 charts. Drugs were found to be the second most common type of medical procedure that could be injurious, involved in 59 out of 255 patient charts that documented a serious adverse event (23%).[2] Five of the 59 drug-related events (8%) were fatal. 

Based on these data, approximately 1.6% of patients admitted to acute care hospitals in Canada experience a serious adverse drug reaction. With almost 2.5 million annual hospital admissions in Canada of the type studied, the statistics suggest that about 40 000 serious adverse drug reactions occur annually in Canadian acute care hospitals.

Some of the adverse drug reactions appeared unavoidable. However, almost half, 28 out of the 59 cases of adverse drug reactions, were considered to have a “certain,” “strong,” or “more than likely” degree of preventability. Three of these preventable cases were fatal. Digoxin toxicity occurred in patients with renal failure in two of the preventable fatalities. In the third case there was inadequate treatment of C. difficile colitis following antibiotic therapy. 

The published details of these cases of preventable adverse drug reactions hint at the causes of the events.[2] In the opinion of this author, most appear to have been simple acts of omission or commission.

• Patients were prescribed medication with a common side effect that could make the underlying condition worse (7/28 cases), e.g., “worsening of renal failure because of renal toxicity related to prescription of multiple medications.”

• Wrong dose (6/28 cases), e.g., “patient overmedicated with benzodiazepine and had seizure after drug suddenly stopped.”

• Inadequate treatment of an adverse drug reaction (2/28 cases, one fatal), e.g., “delayed treatment of digoxin toxicity in patient with acute renal failure, diarrhea and dementia.”

• Inadequate monitoring (3/28 cases), e.g., “delirium secondary to aminophylline toxicity. No measurement of drug level in clinical context of renal failure.”

• Prescription of renally excreted drugs in patients with chronic renal failure (3/28 cases, one fatal), e.g., “digoxin toxicity in patient with chronic renal failure possibly contributed to death.”

There are basic strategies that must be remembered. Monitor the serum levels of toxic drugs more frequently. Monitor renal function in patients receiving drugs excreted renally. Try to avoid adding a sedating drug if the patient already has CNS depression. Dose appropriately.

Yet these precautions are not enough, as there is nothing new in them. Technological system solutions, such as automated dose checking and automated monitoring reminders, may help when they are available. Most of the problems, however, were not system problems. Participation is required at the level of the individuals involved. The solution demands an attitude shift: a change from old-style thinking that drug toxicity is just a capricious and unavoidable minor irritation to the realization that drug-related pain, disability, and fatalities are serious—and often preventable.

The incidence of serious adverse drug reactions in hospitalized patients has not noticeably improved in the past 35 years.[3] It is time to take adverse drug reactions seriously!

—Barbara Cadario, BSc(Hon), BScPhm, MSc
BC Drug and Poison Information Centre

References

1. Baker GR, Norton PG, Flintoft V, et al. The Canadian Adverse Events Study: The incidence of adverse events among hospital patients in Canada. CMAJ 2004;170:1678-1686. PubMed Abstract Full Text
2. Baker GR, Norton PG, Flintoft V, et al. The Canadian Adverse Events Study: The incidence of adverse events among hospital patients in Canada. CMAJ 2004;170:E-appendix 3: Brief description of clinical details of adverse events occurring in 255 patients, by corresponding maximum degree of preventability. Available from: www.cmaj.ca/cgi/content/full/170/11/1678/DC3. Accessed 10 November 2004.  
3. Lazarou J, Pomerantz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients. JAMA 1998;279:1200-1205. PubMed Abstract Full Text