Local Anesthetic Infusion Pump Systems Adverse Events Reported to the Food and Drug Administration

The following are unedited reports from the Medical Device Reporting database.

This report describes four patients. Bupivacaine and adrenaline were infused after total knee procedures. Two patients experienced full thickness sloughs that required plastic surgical intervention and a second procedure with a gastric flap. Two additional patients experienced partial thickness sloughs in the same area, which required split thickness grafts and prolonged nursing and rehabilitation.

The pump was attached at the end of surgery for bunionectomy to a healthy 26-yr-old woman. The catheter was placed under the skin and attached to the infusion device (plain Marcaine [AstraZeneca Pharmaceuticals LP, Waltham, MA] was used). This device automatically delivers 2 ml/h continually until the pump is empty. The continuous infusion of this fluid over time caused swelling, pain, and blistering due to cell death. There was ischemic necrosis of the blister with a full-thickness loss of tissue (slough) down to the bone with a question of osteomyelitis. Wound culture was positive for a staphylococcal species. This patient required hospitalization and was sent for wound débridement and intravenous antibiotics. She may require skin grafting.

The surgeon placed the pump during a gastrectomy with one regular catheter and one soaker catheter in a 77-yr-old man. A serious infection developed that seemed to originate at the catheter point of entry. The device was in place for approximately 4 days. A severe infection and dehiscence resulting in evisceration developed in the patient. This patient required intervention for a life-threatening adverse event and had to undergo repeated surgery.

Table 1summarizes characteristics of 40 patients and adverse events from 34 reports to the FDA. These reports described a variety of infusion pump system models manufactured by three companies. Information on patient sex and age was usually not provided. Most surgeries were orthopedic (45.0%), typically total knee. The second most common procedure was for podiatric surgeries (20.0%), including bunionectomies, plantar fasciotomy, and others. The most commonly reported adverse event (42.5%) was tissue necrosis. The drug(s) infused were not reported in most cases (60%), but in the 16 reports that did specify, 9 were bupivacaine and adrenaline and 7 were bupivacaine only. In these 16 cases, necrosis was no more likely when both bupivacaine and adrenaline were reported than when bupivacaine alone was reported (exact test, P = 0.20). There were also numerous reports for wound infections and systemic infection.

The FDA received 34 reports describing 40 patients with adverse events that occurred during the use of pump systems for direct anesthetic infusion into a surgical wound. The most commonly reported complication was tissue necrosis, an adverse event almost never seen after normal procedures. The consequences of these adverse events were typically severe and required intervention and additional medical and surgical treatment. There were also numerous cases of wound infection reported, but these data do not permit us to assess the incidence of this adverse event, so it is not possible to determine whether these infections were above the expected background rate.

We reviewed the literature and found only one case series, published as a letter, that described complications associated with the use of pump systems for direct anesthetic infusion. This case series describes plastic surgery consultations for three patients referred by the same orthopedic surgeon after knee arthroplasties. 8Two patients needed wound débridements and gastrocnemius flaps, and the third patient underwent repeated débridements and skin grafting. The likely cause of wound ischemia and necrosis was thought to be the infusion of bupivacaine with epinephrine. Reportedly, there was adequate drainage of the wound and no apparent compartment compression. The authors of the letter speculate that the adverse events were related to continuous infusion of epinephrine and subsequent vasoconstriction of the area. In adverse event reports to the FDA, some reports described similar adverse events with use of anesthetic infusion alone. These reports did not explicitly state that epinephrine was not used, and it is possible that epinephrine was used and was not mentioned in the report.

Limitations in Medical Device Reports or MedWatch data should be acknowledged. Device manufacturers, user facilities, and voluntary reporters submit reports to the FDA that are entered into an adverse events database. Accuracy and completeness of reports are not verified by the FDA. The reports do not establish a causal link between a device and an injury or patient problem. Because infection or necrosis may occur after surgery in the absence of continuous anesthetic infusion, it is not possible to definitively conclude that the reported necrosis or infections after surgery was due to infusion pump use, nor is there certainty that continuous infusion of bupivacaine or bupivacaine in combination with epinephrine caused these adverse events. Nevertheless, the reports provide a potentially important signal, suggesting the need for further investigation of the relation between use of pumps for direct continuous infusion of anesthetics and other drugs into surgical wounds and tissue necrosis, serious infections, or cellulitis.

Medical providers and consumers may report adverse events to manufacturers or directly to the FDA through MedWatch.‡§