Author | Study design | Population | Intervention | Control | Outcomes |
---|---|---|---|---|---|
Bischoff et al. [23] | Randomised, placebo-controlled, double-blind trial. 2 arm trial. Sponsorship: none. | N = 250 (2 groups of 125); female (%), 57.6%/57.6%. Age 47 years (SD17)/47 years (SD15). Surgery: 32 different kinds of operation, most frequent being hernias, cholecystectomy, strumectomy, mastectomy, appendectomy and haemorrhoid operations | Benzodiazepine, lormetazepam, oral. Lormetazepam 2 mg PRN, nightly for 5 nights | Placebo, oral. Placebo PRN, nightly for 5 nights | 1. Pain 100 mm VAS (completed in the am regarding degree of pain experienced during the night, every morning for 5 days)2. Analgesic use 3. Sleep quality 100 mm VAS -Total sleep duration (patients AX) -Sleep latency (min) -Awakenings (no.) -Feeling of freshness on awakening (100 mm VAS) |
Blumenkopf [31] | Randomised, placebo-controlled, single-blind trial. 2 arm trial. Sponsorship: none. | N = 50 (intervention n = 21, control n = 29); Female (%), 36% overall. Age, 42 years (SD13) overall Surgery: spinal surgery. | Benzodiazepine in combination. Diazepam, oral. Diazepam 5 mg orally 3 times daily and baclofen 5 mg on day 1, 7.5 mg on day 2 and 10 mg on day 3 Access to promethazine hydrochloride 25 mg, plus meperidine hydrochloride 1 mg/kg q3H, IM as necessary for pain | Usual Care Access to promethazine hydrochloride 25 mg, plus meperidine hydrochloride 1 mg/kg q3H, IM as necessary for pain | 1. Pain 0–10 NRS, measured day 1, 2, 3 post-surgery 2. Narcotic consumption |
Bourne et al. [32] | Randomised, placebo-controlled, double-blind trial. 2 arm trial. Sponsorship: Sheffield Teaching Hospital Department of Pharmacy and Medicines Management. | N = 25 (intervention n = 13, placebo n = 12); female (%), 42%/67%. Age, 58.7 years (SD12.5) /69.9 years (SD12) Surgery: tracheostomy. | Melatonin, oral. 10 mg oral liquid melatonin, administered at 21:00 h for 4 nights | Placebo, oral. 10 mg liquid placebo, administered at 21:00 h for 4 nights | 1. Richards Campbell Sleep Questionnaire -Sleep efficiency measured with EEG (and evaluated for agreement and reliability with actigraphy), measured at nights 3 and 4. |
Egan et al. [27] | Randomised, placebo-controlled, double-blind trial. 2 arm trial. Sponsorship: none. | N = 40 (2 groups of 20); female (%), 100%/100%. Age, 42.9 years (SD12.2) /49.6 years (SD14.5). Surgery: abdominal total hysterectomy. | Benzodiazepine, midazolam IV. 0.125 mg midazolam. Access to PCA pump containing morphine 1 mg on demand (lockout period 8 min) | Placebo infusion.Access to PCA pump containing morphine 1 mg on demand (lockout period 8 min) | 1. Pain 10 cm VAS, measured days 1 and 2 post surgery, between 13:00–15:00 h 2. Level of pain control (morphine) consumed |
Gögenur et al. [33] | Randomised, placebo-controlled, double-blind trial. 2 arm trial. Sponsorship: none. | N = 136 (2 groups of 68); female (%), 68%/74%. Age, 44 years (SD13)/47 years(SD12) Surgery: laparoscopic cholecystectomy | Melatonin, oral. Three capsules of melatonin (each containing 5 mg) Over 3 nights Received 2.5–5.0 mg of Morphine IV. For post-op nausea .625 mg properidol and 1 mg ondansetron IV if necessary. Post discharge 8 mg lornoxicam 2 times a day at 20:00 h and 08:00 h for 4/7 and 5 mg ketobemidon as rescue analgesia | Placebo, oral. Three capsules of placebo (200 mg of lactose and 3 mg magnesium stearate) over 3 nights Received 2.5–5.0 mg of morphine IV. For post-op nausea .625 mg properidol and 1 mg ondansetron IV if necessary. Post discharge 8 mg lornoxicam 2 times a day at 20:00 h and 08:00 h for 4/7 and 5 mg ketobemidon as rescue analgesia | 1. Pain 100 mm VAS, on waking and 20:00 h, on nights 1, 2 and3 post-surgery. 2. Self-reported sleep quality questionnaire 100 mm VAS, in am -Self report sleep quality via sleep diary, completed in am 3. Fatigue 100 mm VAS, on waking and at 20:00 h 4. General wellbeing on 100 mm VAS, on waking and at 20:00 h |
Gong et al. [28] | Randomised, placebo-controlled, single-blind trial. 2 arm trial. Sponsorship: none. | N = 148 (2 groups of 74); female (%), 87%/ 83%. Age, 64.8 years (SD5.3)/66.1 yrs(SD5.9) Surgery: TKR | Non-benzodiazepine Zolpidem, oral. 5 mg zolpidem orally, at bed time for 14 nights Received tramadol 100 mg 3 times a day. Oxycodone and access to acetaminophen tablets (5 mg/325 mg) PRN | Placebo oral, at bed time, for 14 nights Received tramadol 100 mg 3 times a day. Oxycodone and access to acetaminophen tablets (5 mg/325 mg) PRN | 1. Pain 0–10 VAS. Score as recall of previous night, measured at days 1, 3, 5, 7, 11 and14 post-surgery 2. Pain control consumption 3. Sleep Efficiency (PSG) |
Hershberger and Milad [34]. | Randomised, placebo-controlled, double-blind trial. 2 arm trial. Sponsorship: Institutional grant from Dept. of Obstetrics and Gynaecology, Northwestern University Feinberg School of Medicine. | N = 97 (intervention n = 49, placebo n = 48); female (%), 100%/100%. Age, 36 years (SD10)/35 years (SD6). Surgery: ambulatory gynaecological surgeries | Benzodiazepine, lorazepam IV. 1 mg lorazepam IV (single dose, 1 h post-surgery) Access to IV hydromorphone or intramuscular (IM) meperidine or IM fentanyl for pain control | Placebo, IV. 1 mg saline IV (single dose,1 h post-surgery) Access to IV hydromorphone or IM meperidine or IM fentanyl for pain control | 1. Pain 0–10 VAS (number of pain score values recorded varied, but averaged 3, time varied, up to 8 h post op) 2. Narcotic consumption, mg of hydromorphone |
Jacobsen et al. [29] | Randomised, placebo-controlled, double-blind trial. 2 arm trial. Sponsorship: none. | N = 100 (intervention n = 49, placebo n = 51); female (%) 100%/100%. Age, 49.9 years (SD10.5)/50.6 years (SD9.75). Surgery: breast resection, axillary node dissection or mastectomy. | Benzodiazepine, triazolam, oral. 0.125 mg triazolam 3 consecutive nights post op, with option to increase to 0.25 mg after 1 night Received morphine, meperidine, ibuprofen, acetaminophen and/or acetaminophen with codeine, oxycodone or propoxyphene | Placebo, oral. 0.125 mg placebo, permitted an increase to 0.25 mg Received morphine, meperidine, ibuprofen, acetaminophen and/or acetaminophen with codeine, oxycodone or propoxyphene | 1. Sleep quality 100 mm VAS -Estimate TTS/sleep latency (min) -Number of awakenings -100 mm VAS difficulty falling asleep -100 mm VAS how rested they felt in the morning, every morning following 3 nights |
Krenk et al. [24] | Randomised, placebo-controlled, double-blind trial. 2 arm trial. Sponsorship: Lundbeck Foundation Research Grant. | N = 22 (2 groups of 11); female (5%), 50%/70% overall. Age, 70.9 years (SD4.5)/70.5 years (SD5.5). Surgery: fast-track total hip replacement (THR) or total knee replacement (TKR) | Non-benzodiazepine Zolpidem, oral. Oral zolpidem 10 mg, administered 1 h prior to lights-out on day 1 post-op. Received celecoxib 200 mg, slow release acetaminophen 2 g twice daily and 300 mg gabapentin in the morning and 600 mg in the evening. | Placebo, oral. Received celecoxib 200 mg, slow release acetaminophen 2 g twice daily and 300 mg gabapentin in the morning and 600 mg in the evening. | 1. Pain 0–100 mm VAS, morning of day 1 2.Narcotics consumed, mg of morphine 3. Subjective sleep quality 0–10 NRS -Objective sleep measures including TST, sleep period time (SPT), awake time (AT) 4. Fatigue 0–10 NRS |
Nott et al. [26] | Randomised, placebo-controlled, double-blind trial. 4 arm trial. Sponsorship: none. | N = 80 (4 groups of 20); female (%): 0%/0%/0%/0%. Age, 71.7 years (SD9.8)/75.5 years (SD9.5)/71.2 years (SD8.2)/71.9 years (SD8.9). Surgery: uncomplicated transurethral prostatectomy | Group 1 Benzodiazepine Diazepam, oral. Oral diazepam 4 mg 3 times daily OR Group 2 Benzodiazepine in combination. Diazepam, oral. Oral diazepam and single epidural injection of 10 ml bupivacaine. All groups received IM pethidine 0.05–0.125 mg/kg with prochlorperazine 12.5 mg if needed or dextropropoxyphene 32.5 mg with paracetamol 325 mg | Group 3 Usual care OR Group 4 Usual care. Single epidural injection of 10 ml of bupivacaine All groups received IM pethidine 0.05–0.125 mg/kg with prochlorperazine 12.5 mg if needed or dextropropoxyphene 32.5 mg with paracetamol 325 mg | 1. Pain (during irrigation) 0–2 scale (0 = no sensation, 1 = aware only, 2 = painful), within 2 days post-surgery 2. Narcotic consumption |
Riediger et al. [35] | Randomised, placebo-controlled, double-blind trial. 2 arm trial. Sponsorship: University of Basel. | N = 24 (2 groups of 12); female (%), 63%/54% Age, 76 (SD11.75)/68 (SD10) Surgery: decompression for lumbar spine stenosis. | Benzodiazepine in combination. Midazolam, intranasal spray. 6 mg S-ketamine base and 0.5mcg chitosan-HCL/0.1 mL spray, with 0.75 mg midazolam intranasal unit-dose spray and 0.5mcg chitosan-HCL/0.1 mL per dose and placebo PCA. Received 1 g paracetamol orally every 6 h, access to IV metamizole 1 g rescue medication, 6 h lock out | Placebo 2 mg morphine IV PCA and placebo intranasal spray (saline 0.9% and 0.5mcg chitosan-HCL)Received 1 g paracetamol orally every 6 h Access to IV metamizole 1 g rescue medication, 6 h lock out | 1. Pain 0–10 NRS, measured at 1, 2, 4, 24, 48 and 72 h post-surgery 2. Narcotic consumption |
Sajedi et al. [30] | Randomised, placebo-controlled, double-blind trial. 3 arm trial [Intervention (I), intra-articular (IA), I intramuscular (IM), placebo (P)] Sponsorship: Research Dept. University of Medical Sciences, Isfahan. | N = 75 (3 groups of 25); female (%), 21%/20%/12%. Age, 26.9 years (SD5.4)/27.6 years (SD4.7)/27.5 years (SD5.1). Surgery: knee arthroscopy. | Group 1-IA (Benzodiazepine, midazolam intravenously (IV)). Midazolam (75mc/kg) and intra-articular isotonic saline (single dose) Access to inhalation of isoflurane (1–2%) and morphine (0.1 mg/kg) as additional anaesthesia OR Group 2-IV Benzodiazepine, midazolam intra-articular (IA). Midazolam (75mc/kg) and 10 cc IV isotonic saline (single dose) Access to inhalation of isoflurane (1–2%) and morphine (0.1 mg/kg) | Placebo IV and IA Access to inhalation of isoflurane (1–2%) and morphine (0.1 mg/kg) | 1. Pain 0–10 VAS, at 2, 4, 8, 12 and 24 h 2.Analgesic consumption over 24 h |
Singh et al. [36] | Randomised, placebo-controlled trial. 3 arm trial. Sponsorship: none. | N = 105 (3 groups of 35); female (%), 60%/63%/54% Age, 40 years (SD6.27)/38 years (SD7.11)/39 years (SD6.27). Surgery: upper abdominal surgery | Group 1 Benzodiazepine, diazepam, IM. Diazepam 10 mg IM (single dose) OR Group 2 Benzodiazepine, diazepam, IM. Diazepam 5 mg and morphine 5 mg, IM (single dose) | Morphine, IM. Morphine 10 mg IM (single dose) | 1. Pain estimated by patient, 0–4 scale at 30, 60, 90 and120 min post-surgery -pain estimated by observer, 0–4 scale at 30, 60, 90 and 120 min post-surgery |
Tashjian et al. [25] | Randomised, placebo-controlled, double-blind trial. 3 arm trial. Sponsorship: none. | N = 68 (intervention n = 24, control n = 24, placebo n = 19); female (%), 21%/26%/38% overall. Age, 49.2 years/47.5 years/47 years Surgery: knee arthroscopy. | Group 1 Non-benzodiazepine in combination Zolpidem, oral. 7 zolpidem tartrate tablets (10 mg) 40 hydrocodone/acetaminophen bi-tartrate tablets (7.5 mg/750 mg) for the first 7 postoperative days. Access to Ibuprofen 800 mg PRN | Group 2 Placebo, oral. Placebo and 40 hydrocodone/acetaminophen bi-tartrate tablets (7.5 mg/750 mg) Access to Ibuprofen 800 mg PRN OR Group 3 Usual care 40 hydrocodone/acetaminophen bi-tartrate tablets (7.5 mg/750 mg) Access to ibuprofen 800 mg PRN. | 1. Pain 0-10 VAS measured morning and night for first 7 days 2. Pain control (hydrocodone/acetaminophen) consumed 3. Fatigue 0–10 VAS, measured morning and night for first 7 days |
Tompkins et al. [22] | Randomised, placebo-controlled, double-blind trial. 2 arm trial. Sponsorship: Smith & Nephew. | N = 29 (intervention n = 13, control n = 16); female (%), 38%/56%. Age, 36.9 years/35.6 years. Surgery: primary arthroscopic ACL reconstruction. | Group 1 Non-benzodiazepine Zolpidem, oral. Zolpidem tartrate tablets (10 mg) taken for the first 7 post-operative days, taken nightly OR Group 2 Non-benzodiazepine in combination Zolpidem, oral. Oral zolpidem and 40 hydrocodone/acetaminophen bi-tartrate 7.5 mg, to be taken 1–2 tablet every 6 h PRN | Group 3 Placebo, oral OR Group 4 Placebo, oral. Placebo and 40 hydrocodone/acetaminophen bi-tartrate 7.5 mg, to be taken 1–2 tablet every 6 h PRN | 1. Pain 0–100 VAS, measured in the morning and evening days 1–7 post-surgery 2. Narcotic consumed, vicodin (and ibuprofen) 3. Fatigue 0–100 VAS, measured in morning and evening days 1–7 post-surgery |