Table 2.
Study Characteristics Related to Description of Intervention, Control, and Outcomes
| Author, Year | No. of Randomized Patients in Intervention and Control | Description of Intervention | Dose | Description of Control | Measured Outcomes |
|---|---|---|---|---|---|
| Eide, 199438 | I:8 C:8 (cross-over study) |
Ketamine (0,15 mg/kg), morphine (0.075 mg/kg) or saline (9 mg/mL NaCl) were given IV | Intravenous - Ketamine 0.15 mg/kg injected in 10 minutes or Morphine. | Saline solution | Assessment of allodynia, wind-up-like pain, tactile and thermal sensibility and pain, using VAS. |
| Max, 199539 |
I:8 C:8 (cross-over study) |
For 3 days, patients were given 2 hours of intravenous ketamine, alfentanil or placebo. If no pain relief after 60 minutes, the infusion rates were doubled at this time and again at 90 minutes. | Intravenous - Ketamine 0.75 mg/kg/h, can get doubled. Alfentanil 1.5 mcg/kg/min, can get doubled. | Saline solution – 0.375 mL/kg/h | Background pain and mechanical allodynia, each rated every 10 minutes on a VAS. At 10 minutes intervals, the side-effects were asked. |
| Mercadante, 200040 | I:10 C:10 (cross-over study) |
On 3 separate days, patients received ketamine hydrochloride 0.25 mg/kg, 0.50 mg/kg, or saline solution as a slow intravenous bolus administered in 30 minutes. | Intravenous - Ketamine 0.25 mg/kg or 0.5 mg/kg, administered in 30 minutes. | Saline solution | Pain intensity; nausea and vomiting, drowsiness, confusion, and dry mouth; MMSE; arterial blood pressure and side effects. |
| Lauretti, 200241 | I: 10 (3 excluded) C:13 |
At intervention group was given 0.1 mg/kg ketamine (2 mL) in 1% lidocaine solution. At control Group was given 30 μg clonidine (2 mL) in 1% lidocaine solution. The epidural catheter was maintained for 3 consecutive weeks. The outcomes were assessed weekly. | Epidural catheter - 0.1 mg/kg racemic ketamine in 1% lidocaine solution, followed by 30 mg of 1% lidocaine. (Total dose – 0,3mg/kg/day) |
30 μg preservative-free clonidine (2 mL) in 1% lidocaine solution followed by 30 mg of 1% lidocaine (3mL) (Total dose - 80 μg/day) |
The pain intensity was assessed by a VAS in the days 1, 7, 14 and 21 by the beginning of the study. |
| Kvarnstrom, 200335 | I: 12 C:12 (cross-over study) |
Effects of ketamine 0.4 mg/kg and lidocaine 2.5 mg/kg were investigated. All substances were given intravenously. Two intravenous cannulas were applied, one for the infusion and one for blood sampling. | Intravenous – Ketamine 0.4 mg/kg for 40 minutes | Saline solution | Sensibility to touch, static sensibility, thermal sensitivity and intensity of continuous spontaneous pain using a VAS. Measurements were taken at T:0 and then at T:15, T:45, T:60, T:120, T:150. |
| Lynch, 200536 | Ketamine 22 Amitriptyline 22 Ketamine + Amitriptyline 23 C:25 |
Treatments consisted of four topical creams, containing placebo (vehicle only), 2% amitriptyline,1% ketamine, or a combination of 2% amitriptyline and 1% ketamine. | Topical cream - 1% Ketamine, or 2% amitriptyline + 1% ketamine, 3 times/day for 3 weeks | Topical placebo (vehicle only) | Average daily pain intensity using an 11-point NRS McGill Pain Questionnaire, measures of allodynia and hyperalgesia, and patient satisfaction. |
| Vranken, 200537 | Ketamine 11 (50 mg)/11 (75mg) C:11 |
First, S(C)-ketamine50 mg will be compared with placebo. If S(C)-ketamine 50 mg turns out to be more effective than placebo, S(C)-ketamine 75 mg will be compared to S(C)-ketamine 50 mg. | Iontophoretic administration - Ketamine 50mg or 75mg for 5 days. | Isotonic saline solution – 3mL | Pain intensity measured by VAS, health status (Pain Disability Index and EQ-5D) and quality of life (SF-36). |
| Tonet, 200842 | I: 10 amitriptyline + carbamazepine + ketamine C: 13 amitriptyline + carbamazepine. |
In the first group received amitriptyline (25 mg) + carbamazepine (600 mg) + ketamine (30 mg/day) patients in the second group amitriptyline (25 mg/day) + carbamazepine (600 mg/day). When there was a need for analgesic supplementation, codeine (30 mg) was administered. | Oral - Ketamine 30 mg/ day, for 4 weeks. | Amitriptyline 25 mg + carbamazepine 600mg | The patients were evaluated for pain intensity, weekly for four weeks, using the numerical pain scale. |
| Sigtermans 200925 | I: 30 C:30 |
Patients were given a 4.2-day intravenous infusion of low-dose ketamine or placebo using an individualized dosage based on effect (pain relief) and side effects (nausea/vomiting/psychomimetic effects). | Intravenous - Ketamine infusion rate started at 1.2 mcg/kg.min to a maximum of 7.2 mcg/kg.min | Normal saline solution | Spontaneous pain assessed by a NRS. Radboud Skills Questionnaire (RASQ) and the Walking Ability Questionnaire (WAQ); active range of motion, threshold for touch; skin temperature and volumetric measurements. |
| Schwartzman 200926 | I: 9 C: 10 |
Infusion of 100 mL of normal saline with or without ketamine for 4 h (25 mL/h) daily for 10 days (5 days on, 2 days off, 5 days on). First day, infusion was set to 50% of the maximum rate. Second day, the infusion was increased to 75% of the maximum rate. Third day, infusion was increased to the maximum rate and maintained. | Intravenous - Ketamine maximum dose - 0.35 mg/kg/h, not to exceed 25 mg/h. | Normal saline solution | Overall pain level, joint pain, pin hyperalgesia, touch allodynia, cold allodynia and deep pressure evoked pain, strength and facility of movement, McGill questionnaire, quality of life questionnaire and a pain questionnaire, sensory and motor tests were assessed. |
| Amr, 201028 | I: 20 C: 20 (cross-over study) |
Intervention group received 80 mg ketamine over a 5-hour daily for 7 days and 300 mg of gabapentin 3 times daily. Control group received a saline infusion over 5 hours daily for 7 days and 300 mg of gabapentin 3 times daily. | Intravenous -Ketamine 80 mg administered in 5 hours, for 7 days | Isotonic saline 0.9% | VAS for pain was assessed prior to treatment, daily following the infusions for 7 days and one week after infusion termination. Side effects, were reported. |
| Amr, 201127 | I: 20 C: 20 (cross-over study) |
Intervention group received 0.2 mg/Kg of ketamine (2 mL) through epidural injection. Control group received saline solution 0.9%(2 mL) through epidural injection. Both groups received gabapentin 300 mg 3 times/day. | Epidural infusion - 0.2 mg/Kg of preservative-free ketamine 2 mL. | Isotonic saline 0.9% 2mL | VAS for pain obtained pre-injection, 7, 15, 30, 45 and 60 days post injection. Patients were also asked to report any side-effects. |
| Barros, 201229 | I: 12 C: 12 (cross-over study) |
Divided into two groups instructed to apply the ointment on the site of pain four times a day. After 15 days of treatment - washout period of seven days. After the washout period, treatments were inverted and carried out for the same time. | Topical Oinment - Ketamine 1%, during 15 days | Placebo ointment | Numerical Verbal Scale, Measured at the times: M1 – First 15 days of treatment; M2 start of washout; M3 – start of 15 days of crossover treatment; M4 – End of treatment. |
| Niesters, 201330 | I: 10 C: 10 (cross-over study) |
Treatments were as follows: - 1h infusion of 0.57 mg/kg S(+) ketamine; - morphine bolus of 0.05 mg/kg followed by 0.015 mg/kg/h for 1 h; and a 1 h saline solution infusion. | Intravenous – Ketamine 0.57 mg/kg infusion duration of 1 hour | Isotonic saline 0.9% during 1 hour | Spontaneous pain scores were measured by NRS. Subjects were contacted after their treatment to determine the duration of pain relief. And conditioned pain modulation (CPM). |
| Kim, 201531 | I: 15 C: 15 |
Patients were randomly divided into 2 groups of 15 patients each, and ketamine 1 mg/kg or magnesium 30 mg/kg was administered intravenously for 1 hour after midazolam sedation. | Intravenous - Ketamine (1 mg/kg per hour) diluted in 0.9% normal saline to a final volume of 100 mL | Magnesium sulfate (30 mg/kg per hour) were diluted in 0.9% normal saline to a final volume of 100 mL | Pain was rated on a VAS during a 2-week follow-up. All patients also completed the Doleur Neuropathique 4 questionnaire at baseline and final visits. |
| Rigo, 201732 | I: 11 Methadone: 13 Methadone + Ketamine: 13 |
Patients were randomly allocated to receive one of the 3 treatments: 3 mg methadone, 30 mg ketamine, or 3 mg methadone plus 30 mg ketamine 3 times a day. | Oral – Ketamine 3mg during 3 months | Methadone 3mg or Methadone 3mg + Ketamine 30mg | During 90 days, we assessed pain scores using a 10-point VAS, allodynia, burning/shooting pain, and side effects |
| Fallon, 201833 | I: 107 C: 107 |
Randomized in two groups to receive ketamine or placebo across 2 weeks to an effective and tolerable dosage. The starting dosage was 40mg/d, with a maximum400 mg/d. Patients receive a stable dose for 16 days. | Oral – Ketamine 40–400 mg/d, during 2 weeks | Placebo | Duration of analgesic benefit using the Short Form McGill Pain Questionnaire. Mean and worst pain; Hospital Anxiety and Depression Score and serious adverse events. |
| Pickering, 201934 | I: 20 C: 20 (cross-over study) |
Each patient received: placebo /placebo, ketamine /placebo, and ketamine /magnesium, every 35 days. After this, patients returned for the second randomization. They were re-evaluated and randomized if their pain intensity on the day of randomization was like pain intensity at inclusion. The same assessment was done before the third period. | Intravenous – Ketamine 0.5 mg/kg diluted in 45 mL saline solution | Magnesium 3000 mg administered over 30 min | Primary endpoint - area under the curve of daily pain intensity for a period of 35 days after infusion. Secondary endpoints - pain (at 7, 15, 21 and 28 days) and health-related, emotional, sleep, and quality of life questionnaires. |
Abbreviations: I, intervention group; C, control; VAS, visual analogic scale; MMSE, Mini-Mental State Examination.