Open Access(233) Characterization of Confusion, An Adverse Event Associated with Intrathecal Ziconotide Infusion in Chronic Pain Patients
Author(s) -
Webster Lyn,
Henderson Robert,
Katz Nat,
Ellis David
Publication year - 2001
Publication title -
pain medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.893
H-Index - 97
eISSN - 1526-4637
pISSN - 1526-2375
DOI - 10.1111/j.1526-4637.2001.pme01039-32.x
Subject(s) - medicine , confusion , adverse effect , anesthesia , analgesic , psychology , psychoanalysis
Ziconotide is a novel analgesic currently being developed for intrathecal (IT) infusion to patients with chronic, intractable pain. A long‐term safety study has enrolled 586 patients who were titrated to efficacy and treated for up to 180 days. Confusion (COSTART term) is not infrequently observed with ziconotide IT infusion, and is frequently observed with opiates, so it was further characterized. Overall, confusion was observed in 34.3% of patients. Verbatim terms used to describe the observation were fogginess, spaciness, decreased mental alertness, disorientation to time, or mixed up feeling. Confusion occurred with an (mean ± SD) IT infusion rate of 0.30 ± 0.25 (median 0.225) mg/hr (recommended initial IT infusion rate is 0.10 mg/hr). An integrated summary of safety analysis, including trials that forced titration to rates of up to 7.0 mg/hr, revealed that higher IT infusion rates were associated with an increased incidence of all adverse events (AEs), including confusion. In the long‐term safety study, the average time to onset of confusion was 49 ± 52 (median 31) days; it was intermittent in 66% and continuous in 31%. Confusion was judged to be severe in 17% of cases; the decision was made to reduce the dose in 49% and discontinue the infusion in 19% of cases. Confusion represented 3.9% of all serious AEs, defined as life‐threatening or requiring hospitalization. It occurred with increased frequency when CNS depressants were administered concomitantly. The median confusion duration was 6 days, but resolved within 1 day in 1/3 of patients. It is believed to result from supraspinal distribution of ziconotide, occurs at therapeutic IT doses, is reversible, apparently dose‐dependent, mild or moderate in most cases, and does not require cessation of therapy. [This long‐term safety study is ongoing and presently enrolling patients; these results will be updated based on a larger dataset at the time of presentation.]