Surgical adverse events

Because of the problems that resulted from self-regulation, another law, the Dietary Supplement and Non-Prescription Drug Consumer Protection Act, was approved in 2006. This law requires manufacturers, packers, or distributors of supplements to submit reports of serious adverse events to the FDA. Serious adverse events are defined as death, a life-threatening event, hospitalization, a persistent or significant disability or incapacity, congenital anomaly or birth defect, or an adverse event that requires medical or surgical intervention to prevent such outcomes based on reasonable medical judgment. If this requirement were enforced, and consumers cooperated, these reports would make it possible to identify trends in adverse effects and would help to alert the public to safety issues. 

No doubt in part because of ethical controversies it has sometimes been difficult to mount adequate controlled studies, especially in the USA. Many women and practitioners have retained a preference for dilatation and evacuation as a means of performing abortion rather than using a medicinal technique. In a pilot study at Chapel Hill, North Carolina oral mifepristone 200 mg followed 2 days later by vaginal and oral misoprostol was compared with the surgical method (11). Of 47 women eligible for the trial, 29 declined to participate, primarily because of a preference for dilatation and evacuation. Of the 18 participants enrolled, nine were randomized to treatment with mifepristone + misoprostol and 9 to dilatation and evacuation. Mifepristone + misoprostol caused more pain and adverse events, although none was serious.)... 

The first in human trial (FIH) for cell-based therapies is in patients often with no available alternative therapies rather than in normal volunteers. These are also populations where clinical effects are less easy to manifest themselves and where adverse events may be difficult to distinguish from disease-associated events. The surgical procedures and use of immunosuppressants may also contribute to the adverse event profile. Therefore it is even more important to understand the nature and extent of the pathological process underlying the disease symptoms of the patients enrolled in the early clinical trials. 

The Vitrasert has proved to be safe and effective for treatment of CMV retinitis as an adjimct to continued systemic therapy. Although use of the Vitrasert is relatively safe, it is not free of complications. Adverse events can occur in 10% to 20% of patients and can result in significant loss of vision. Acute and long-term complications associated with the Vitrasert or its surgical procedure include retinal detachment, vitreous hemorrhage, and endophthalmitis. 

One of the most common adverse events associated with the type of treatment is ocular hypertension. In one study intravitreal injections of 25 mg triamcinolone acetonide resulted in ocular hypertension in approximately 50% of treated eyes, commencing 1 to 2 months after the injection. lOP was responsive to topical therapy and normalized after approximately 6 months after the injection. Other studies reported that patients who feiled medical therapy required surgical intervention to reduce iatrogenic pressure elevations. 

Morphi Dex contains morphine sulfate and dextromethorphan in a 1 1 ratio. Double-blind, single-dose analgesic efficacy studies in over 800 patients with post-surgical pain have shown superior analgesic activity for the combination (60 60 mg) than separate doses of the individual components (28,29). In double-bhnd, multiple-dose studies in 321 patients with chronic pain the combination provided satisfactory pain control with a significantly lower mean daily dose of morphine sulfate. Other studies have shown similar responses (28) and an adverse events profile similar to that of a similar dose of morphine sulfate (30). The most common adverse events seen in a multiple-dose, non-placebo-controlled study in 1400 subjects were nausea, dizziness, vomiting, somnolence, confusion, and pruritus. There was a significant trend toward lower incidence of constipation with the combination than with morphine sulfate alone (31,32). 

A population pharmacokinetic study of intramuscular quinine (loading dose 20 mg/kg salt diluted 1 1 in water) in 120 Ghanaian children with severe malaria showed predictable profiles, which were within the target range for quinine (15-20 pg/ml) and independent of clinical and laboratory variables (1). Adverse events included skin induration or abscesses at the injection site (12%), all of which resolved without surgical intervention, and hypoglycemia (10%), a special risk in children who were hypoglycemic at presentation. 

Only three of 422 patients treated with a single dose of teicoplanin for antimicrobial prophylaxis during hip or knee arthroplasty (400 mg by intravenous bolus at the time of anesthesia) reported adverse events compared with nine of 424 patients treated with five doses of cefazo-line one had nausea and two had erythema (7). Six patients given teicoplanin had surgical wound infections, and 57 had proven or suspected infections involving other body systems. 

CAPTURE has reported outcomes on 2,500 high-surgical-risk patients treated using the Guidant filter and stent system at 137 centers across the United States, 90.7% of whom were asymptomatic (49). The 30-day major adverse event rate (death, stroke, myocardial infarction) for asymptomatic patients (n = 2268) was 4.9% and for asymptomatic patients under the age of 80 years (n = 1741) was 4.2%. Moreover, if only the 30-day rate of stroke and death is considered the event rate fell to 3.6% in asymptomatic patients under the age of 80 years. Lastly, CASES-PMS enrolled 974 asymptomatic high-surgical risk patients who were treated with Cordis/Johnson 8c Johnson stent and filter system (50). The 30-day risk of stroke and death in the entire asymptomatic group was 4.2% (the breakout for patients under 80 years of age is unavailable). 

It was noted, however, that 3 of the 20 treated patients developed sudden severe vitreous hemorrhage, which led to functional blindness and therefore the authors advised caution with use of this treatment. Vitreoretinal surgical techniques have improved significantly since this report and it is possible that such adverse events could be more easily managed at this time. 

All six surgical events were successfully treated with rhAT, as shown by the absence of clinical evidence of thrombosis for these patients that all had an history of thromboembolism. In two patients, where initial pre-and post-treatment levels were available, there was a 1.69 and 1.66% per U per kg increase, which is similar to the 1.39 and 2.05% per U per kg reported for hpAT. There was no clinical evidence of thrombosis or bleeding, and no adverse events related to the drug were reported. Four of the six surgical events were fol-lowed-up by vascular duplex ultrasound of the lower extremities, with no clinical evidence of acute thrombosis (Table 11.4). Four of the five patients, who receive multiple doses of rhAT, were also screened for antibody formation against rhAT several weeks postoperatively. None of the patients developed detectable antibodies to the rhAT. 

Retrospective reviews of medical records aim to assess the nature, incidence and economic impact of adverse events and to provide some information on their causes. Adverse events are defined as an unintended injury caused by medical management rather than the disease process that results in some definite injury or, at the very least, spent on additional days in hospital (Box 4.1). Definitions are critical in patient safety and one has to be constantly aware of differences in terminology. For instance, a study by Andrews et al. (1997) in the United States showed a 17.7% rate of serious adverse events in a surgical unit, much higher than most other studies. However, their definition of adverse event was different from that usually employed and they used observation rather than record review, as most other studies do. These are not flaws the study is a good one. The point is... 

A significant percentage of adverse events are associated with a surgical procedure. For instance, in the Utah Colorado Medical Practice Study, the annual incidence rate of adverse events amongst hospitalized patients who received an operation was 3%, of which half were preventable. Some operations, such as extremity bypass graft, abdominal aortic aneurysm repair and colon resection, were at particularly high risk of preventable adverse events (Thomas et al, 2000b Thomas and Brennan, 2001). 

Another approach to examining mortality rates is through professionally led national audits. The Scottish Audit of Surgical Mortality (SASM) for instance, uses case assessment applying proformas that are voluntarily filled by clinicians and then examined by clinical assessors to determine the reasons for the death. SASM has shown that cases in which an adverse event contributed to death have steadily reduced over the years, suggesting that efforts by SASM and others to increase involvement of consultants in decision making and improve interaaion between surgical, anaesthetic and ITU teams have borne fruit. 

Other common types of adverse events in hospitals are preventable infections, surgical and diagnostic mistakes, and events involving equipment use. Two million patients are estimated to acquire infections in the hospital each year, and 25-70 percent of these infections are preventable 90,000 of the affected individuals die (Centers for Disease Control and Prevention, 1996 Weinstein, 1998 Haley and others, 1985). Between 87,500 and 350,000 patients are exposed to life-threatening infections every year because of hospital-acquired bloodstream infections alone (Wenzel and Edmond, 2001). 

Patients who received daptomycin for surgical site infections have been assessed in the US Cubicin Outcomes Registry [131 ]. Among 118 subjects who received daptomycin for a mean duration of 14 days, 8 had nine adverse events that were possibly related to daptomycin one raised CK activity and myalgia four raised CK activity and one case each of pruritus, vomiting, myalgia, and increased creatinine. CK activity was raised overall in 4%. 

Complications are classified into minor and major adverse events. Minor adverse reactions are defined as unexpected or undesirable clinical occurrences that require no immediate or delayed surgical intervention (McGraw et al. 2002). A major adverse event is defined as the occurrence of an unexpected or undesirable clini-... 

Although opioid dose requirements are reduced with short-term use of NSAIDs including naproxen, it remains unclear whether reductions in dose are associated with a decrease in opioid-related adverse events such as nausea, vomiting, and constipation. Like other nonselective NSAIDs, naproxen is often withheld in the peri-operative period for fear of surgical site and GI bleeding. It should be appreciated that unlike aspirin, inhibition of platelet aggregation with naproxen is reversible, and temporally related to serum drug concentration. 

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