title: Analgesic effects of ketamine infusion therapy in korean patients with neuropathic pain: A 2-week, open-label, uncontrolled study.
abstract: BACKGROUND
  The overexcitation of the N-methyl-D-aspartate receptor complex appears to play a critical role in the development of neuropathic pain, and ketamine acts as an antagonist to that receptor. Some publications have reported on the prominent relief of neuropathic pain with intravenous or subcutaneous ketamine infusions or a single-dose intravenous ketamine injection despite adverse effects.
  
  
  OBJECTIVE
  The primary objective of this study was to determine the analgesic effect of intravenous ketamine infusion therapy for neuropathic pain refractory to conventional treatments. Secondary objectives included identifying the variables related to the analgesic effect and the pain descriptors susceptible to ketamine infusion.
  
  
  METHODS
  This 2-week, open-label, uncontrolled study was conducted in Korean patients with neuropathic pain recruited from the Samsung Seoul Hospital (Seoul, Republic of Korea) outpatient pain management unit. Patients were required to have a pain severity score >5 (visual analog scale [VAS], where 0 = no pain and 10 = worst pain imaginable) over a period of ≥1 month while on standard treatment. The patients were required to have shown no benefit from standard treatment and no pain relief lasting over 1 month. The ketamine infusion therapy was composed of 3 sessions performed consecutively every other day. Midazolam was administered concomitantly to reduce the occurrence of central nervous system-related adverse events (AEs) secondary to ketamine. Each session was as follows: ketamine 0.2 mg/kg and midazolam 0.1 mg/kg were administered intravenously for 5 minutes as a loading dose, followed by a continuous infusion of ketamine 0.5 mg/kg/h and midazolam 0.025 mg/kg/h for 2 hours. AEs were assessed in the following ways: close monitoring of ECG, blood pressure, oxygen saturation, and evaluating the need for treatment of AEs during infu- sion and until discharge by an attending anesthesiologist; an open question about discomfort at the end of each session; spontaneous reports about AEs during each session; and the patients' and caregivers' checklist of AEs occurring at home for 2 weeks after discharge. All the descriptors of pain expressed by the patients in Korean were recorded and translated into appropriate English terminology on the basis of the literature on Korean verbal descriptors of pain. Each of the translated pain descriptors was then classified into 1 of 18 sensory items.
  
  
  RESULTS
  The overall VAS score for pain decreased from a baseline mean (SD) of 7.20 (1.77) to 5.46 (2.29) (P < 0.001) 2 weeks after treatment in 103 patients (53 males and 50 females; mean age, 52.56 [17.33] years) who completed the study. Variables such as age, sex, and the duration and diagnosis of pain were not found to be associated with analgesic effect. Seven of the 18 pain descriptors were found to have a significant response to ketamine infusion treatment between baseline and 2 weeks follow-up: burning pain (P = 0.008); dull, aching pain (P < 0.001); overly sensitive to touch (P = 0.002); stabbing pain (P = 0.008); electric pain (P = 0.031); tingling pain (P < 0.001); and squeezing pain (P < 0.001). A total of 52 patients reported AEs: 33 during infusion and 44 during recovery and up to 2 weeks follow up. The most commonly reported AEs were snoring (15 [15%]) during infusion and dizziness (43 [42%]) during recovery.
  
  
  CONCLUSIONS
  Ketamine infusion therapy was associated with reduced severity of neuropathic pain and generally well tolerated for up to 2 weeks in these patients with neuropathic pain refractory to standard treatment. Variables such as sex, age, and the diagnosis and duration of pain had no association with the analgesic effect of this treatment. Randomized controlled trials are needed to evaluate the efficacy and tolerability of treatment with ketamine infusion.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Samsung Seoul Hospital, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jin Gu
authors.initials: JG
authors.lastname: Kang
authors.affiliation: Department of Anesthesiology and Pain Medicine, Samsung Seoul Hospital, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Chul Joong
authors.initials: CJ
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology and Pain Medicine, Samsung Seoul Hospital, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Tae Hyeong
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Samsung Seoul Hospital, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Woo Seok
authors.initials: WS
authors.lastname: Sim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Samsung Seoul Hospital, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Byung Seop
authors.initials: BS
authors.lastname: Shin
authors.affiliation: Department of Anesthesiology and Pain Medicine, Samsung Seoul Hospital, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Francis Sahngun
authors.initials: FS
authors.lastname: Nahm
authors.affiliation: Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Pyung Bok
authors.initials: PB
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sang Chul
authors.initials: SC
authors.lastname: Lee
keywords: infusion therapy; ketamine; neuropathic pain; pain descriptor