GRAPEVINE, TEX. – Risks associated with cryolipolysis for fat reduction are mostly transient and generally mild, according to a recent analysis.
"Severe pain" was reported in approximately 0.05% of all treated patients, said Dr. Nazanin Saedi of the University of California, Irvine.
Reports of severe pain emerged in postmarket surveillance, which traditionally allows for the detection of rare side effects not seen in clinical trials. Of more than 60,000 cryolipolysis treatments between June 2009 and December 2010, there were 23 reports of "severe pain" associated with the Zeltiq system.
The determination that a report was of "severe" pain rather than the known potential discomfort following treatment depended on symptoms. Of the reports, 11 were described as "severe," 8 as "sensitive to touch," 6 as "stabbing," and 6 as "deep/severe burning." (Patients could report more than one symptom). The incidence was calculated based on a denominator of 50,000, giving a rate of 0.00046, or 0.05%.
Zeltiq evaluated the "severe pain" to understand its etiology. The pain does not appear to be associated with the increasing number of larger applicators, because 10 of the 23 of patients reporting "severe pain" underwent treatment with the smaller applicator, Dr. Saedi noted.
Most severe pain involved the abdomen (21 of the 23 patients), arising at a mean of 3.4 days (range, 1-7) following the procedure. The mean time to resolution was 13.9 days (range, 7-28). Just one patient had severe pain lasting for 28 days, while in the majority (16 of the 23), pain had resolved by 2 weeks. Six patients reported that the pain worsened before getting better, peaking at about a week.
Two of the patients had known connective tissue disease, while the etiology was unknown for the rest. Exaggerated panniculitis is one possibility. The pain might also be of focal neuropathic origin, including allodynia, hyperneuralgia, or nerve inflammation arising from cytokine-mediated irritation of nerve fibers during the onset of inflammation following the procedure, said Dr. Saedi. It is likely that there are multiple etiologies.
A variety of therapeutic measures were used to treat the severe pain, but only the topical lidocaine patch was consistently reported as being helpful. Compression garments, lidocaine/tetracaine cream, and Vicodin (hydrocodone bitartrate and acetaminophen) were reported to have some effect, while ibuprofen, Percocet (oxycodone HCl and acetaminophen), Tylenol (acetaminophen) with codeine, ice, and heating pads had little or no effect, Dr. Saedi said.
Hyperpigmentation associated with a first- or second-degree burn of the dermis was another rare adverse event that arose in postmarketing surveillance. A total of four cases were reported, or less than 0.01% of treated patients. Three of the four were deemed to have been a result of operator error. All cases resolved.
Cryolipolysis technology uses controlled cold exposure to reduce subcutaneous fat. Adipocytes are selectively damaged via control and modulation of the cold exposure, while avoiding damage to the overlying epidermis and dermis. The decrease in fat thickness occurs gradually over the subsequent 3 months, and is most pronounced in patients with limited, discrete fatty bulges. The novel technology is among the noninvasive mechanisms for fat reduction that are becoming increasingly popular commercially, she noted.
Since the reports, there have been changes to the user manual as well as revisions in user training, user interface, and procedure monitoring , which make the likelihood of burn injury or subsequent hyperpigmentation more unlikely, even in the event of misuse. In fact, there have been no further reports of burn injury or hyperpigmentation during the last 30,000 procedure cycles, she noted.
"Further postmarket surveillance is needed to identify and better understand rare events," Dr. Saedi concluded.
Dr. Saedi said that she had no relevant financial disclosures. However, her coinvestigators are on Zeltiq's advisory board and have received educational and research support and honoraria from the company.