The effect of oral dexamethasone on duration of analgesia after upper limb surgery under infraclavicular brachial plexus block: a randomised controlled trial.

The effects of oral dexamethasone on peripheral nerve blocks have not been investigated. We randomly allocated adults scheduled for forearm or hand surgery to oral placebo (n = 61), dexamethasone 12 mg (n = 61) or dexamethasone 24 mg (n = 57) about 45 min before lateral infraclavicular block. Mean (SD) time until first pain after block were: 841 (327) min; 1171 (318) min; and 1256 (395) min, respectively. Mean (98.3%CI) differences in time until first postoperative pain for dexamethasone 24 mg vs. placebo and vs. dexamethasone 12 mg were: 412 (248-577) min, p < 0.001; and 85 (-78 to 249) min, p = 0.21, respectively. Mean (98.3%CI) difference in time until first postoperative pain for dexamethasone 12 mg vs. placebo was 330 (186-474) min, p < 0.001. Both 24 mg and 12 mg of oral dexamethasone increased the time until first postoperative pain compared with placebo in patients having upper limb surgery under infraclavicular brachial plexus block.

Effect of a single pre-operative 125 mg dose of methylprednisolone on postoperative delirium in hip fracture patients; a randomised, double-blind, placebo-controlled trial.

Postoperative delirium is common after hip fracture surgery, and may have a neuro-inflammatory cause. We conducted a single-centre, randomised, double-blind, placebo-controlled trial of 117 older hip fracture patients to see if a single, pre-operative intravenous dose of 125 mg methylprednisolone could reduce the severity and/or incidence of postoperative delirium, assessed using the Confusion Assessment Method delirium severity score. Modified intention-to-treat analysis found no significant difference in our primary outcome, median (IQR [range]) cumulative Confusion Assessment Method delirium severity score over the first three postoperative days between the methylprednisolone and placebo groups (1 (0-6 [0-39]) vs. 2 (0-10 [0-32]), p = 0.294). Both the prevalence of postoperative delirium (Confusion Assessment Method delirium severity score ≥ 5, 10/59 vs. 19/58, p = 0.048) and the median (IQR [range]) cumulated postoperative (by day 3) fatigue scores (5 (2-6 [0-11]) vs. 6 (4-8 [0-16]), p = 0.008) were significantly lower in the methylprednisolone compared with the placebo group. There were no significant between-group differences in the rate of completing physiotherapy, postoperative pain, the administration of antipsychotic drugs, infection, length of inpatient stay or 30- and 90-day mortality. No major adverse reactions related to methylprednisolone were recorded. We conclude that a single, pre-operative dose of 125 mg methylprednisolone does not reduce the severity of postoperative delirium, but may reduce both the prevalence of delirium and the severity of fatigue after hip fracture surgery in older patients, enabling remobilisation and recovery.

Preoperative ultraviolet B inflammation in skin: Modelling individual differences in acute postoperative pain and neuro-immune interactions.

BACKGROUND: Neuroimmune interactions play a vital role in many of the most common pain conditions, such as arthritis. There have been many attempts to derive clinically predictive information from an individual's inflammatory response in order to gauge subsequent pain perception. OBJECTIVES: Here, we wanted to test whether this effort could be enhanced and complemented by the use of a model system which takes into account the function of not just circulating, but also tissue-resident immune cells: ultraviolet B (UVB) irradiation of the skin. METHODS: We conducted psychophysical and transcriptional analysis of hyperalgesia arising as a result of UVB-induced inflammation in patients before total knee arthroplasty (TKA, n = 23). Levels of acute postoperative pain were assessed and correlated with preoperative data. RESULTS: Cytokine and chemokine responses after UVB irradiation were found to be inversely correlated with the level of pain experienced after surgery (Spearman's ρ = -0.498). CONCLUSION: It may be possible to use this simple model to study and predict the nature of neuro-immune responses at more remote, clinically relevant sites. SIGNIFICANCE: A simple model of UVB inflammation in the skin might predict the degree of a patient's neuro-immune response and the extent of their postoperative pain after total knee arthroplasty.

Chronic pre-operative opioid use and acute pain after fast-track total knee arthroplasty.

BACKGROUND: Pre-operative opioid use has been suggested to increase post-operative pain and opioid consumption after total knee arthroplasty (TKA), but previous studies are either retrospective or inhomogeneous with regard to surgical procedures or control of analgesic regimes, or with few opioid-treated patients, hindering firm conclusions. METHODS: In a prospective observational study, we investigated the effect of > 4 weeks pre-operative opioid use [none vs. low dose (< 30 mg morphine equivalents (eq.)) vs. high dose (> 30 mg morphine eq.] in patients scheduled for primary, unilateral TKA. All patients had well-defined multimodal opioid-sparring perioperative analgesic therapy, and continued any pre-operative opioid medication. The primary outcome was differences between groups in pain at rest and during walk for the first 6 post-operative days. RESULTS: Among 123 patients included, 115 were available for final analysis (93% follow-up rate). Post-operative pain during walk was significantly increased in both opioid-treated groups vs. non-opioid-treated patients (P < 0.009). Secondary analysis of combining all pre-operatively opioid-treated patients vs. opioid-free patients, showed significantly increased pain at rest and walk and increased post-operative opioid requirement - excluding pre-operative dosage - during the first post-operative week in opioid-treated patients (P = 0.001 and P = 0.007, respectively). CONCLUSION: Pre-operative opioid use increases the risk for post-operative pain at rest and walk, and increased opioid consumption after TKA.

Perioperative glucocorticoids in hip and knee surgery - benefit vs. harm? A review of randomized clinical trials.

Glucocorticoids are frequently used to prevent post-operative nausea and vomiting (PONV), and may be part of multimodal analgesic regimes. The objective of this review was to evaluate the overall benefit vs. harm of perioperative glucocorticoids in patients undergoing hip or knee surgery. A wide search was performed in PubMed, Embase, and Cochrane Central to identify relevant randomized clinical trials. A systematic approach was used, starting from the PRISMA recommendations. The Cochrane Collaboration's tool was used for risk of bias assessment. Studies were divided into three groups: systemic glucocorticoid administration analogous to > 10 mg or ≤ 10 mg dexamethasone, and local glucocorticoid administration. Seventeen studies with data from 1081 patients were included in the final qualitative synthesis. Benefit (of any kind) with glucocorticoid vs. placebo was reported in 15 studies. PONV was reduced with systemic glucocorticoid. Pain was reduced with high-dose systemic and local glucocorticoid, but not with low-dose systemic glucocorticoid. Systemic inflammatory markers were reduced with low-dose and high-dose systemic glucocorticoid, and with local glucocorticoid. Functional recovery was improved with local glucocorticoid. All studies were small-sized and none sufficiently powered to meaningfully evaluate uncommon adverse events. Most of the local administration studies had poor scientific quality (high risk of bias). Due to clinical heterogeneity and poor scientific quality, no meta-analysis was performed. In conclusion, in addition to PONV reduction with low-dose systemic glucocorticoid, this review supports high-dose systemic glucocorticoid to ameliorate post-operative pain after hip and knee surgery. However, large-scale safety and dose-finding studies are warranted before final recommendations.

Effect of high-dose preoperative methylprednisolone on recovery after total hip arthroplasty: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: High-dose glucocorticoid may reduce postsurgical pain and improve recovery. We hypothesized that 125 mg methylprednisolone (MP) would reduce time to meet functional discharge criteria after total hip arthroplasty (THA). METHODS: Forty-eight patients undergoing unilateral THA under spinal anaesthesia were consecutively included in this randomized, double-blind, placebo-controlled trial receiving preoperative i.v. MP or saline. All patients received a standardized, multimodal analgesic regime with paracetamol, celecoxib, and gabapentin. The primary outcome was time to meet well-defined functional discharge criteria. Secondary outcomes were handgrip strength and endurance, pain, nausea, vomiting, fatigue, sleep quality, and rescue analgesic-, antiemetic-, and hypnotic medicine requirements. The inflammatory response measured by C-reactive protein (CRP) and actual length of stay were also registered. Discharge criteria were assessed twice daily (at 09:00 and 14:00 h) until discharge. Other outcomes were assessed at 2, 4, 6, 8, and 24 h after operation, and also in a questionnaire from postoperative day (POD) 1-4. RESULTS: Time to meet discharge criteria was [median (IQR) (95% CI), MP vs placebo]: 23.5 (23.3-23.7) (17.8-43.8) vs 23.5 (23.0-23.8) (20.0-46.8) h, the mean difference (95% CI) being -1.3 (-4.7 to 2.2) h, P=0.65. Overall pain for the first 24 h after surgery was significantly reduced in the MP vs the placebo group (P<0.01), as was CRP at 24 h (P<0.0001). No other between-group differences were observed. No drug-related complications were observed at follow-up on POD30. CONCLUSIONS: MP 125 mg i.v. before surgery added to a multimodal oral analgesic regime did not reduce time to meet functional discharge criteria after THA, but improved analgesia for the first 24 h.

Possible effects of mobilisation on acute post-operative pain and nociceptive function after total knee arthroplasty.

BACKGROUND: Experimental studies in animals, healthy volunteers, and patients with chronic pain suggest exercise to provide analgesia in several types of pain conditions and after various nociceptive stimuli. To our knowledge, there is no data on the effects of exercise on pain and nociceptive function in surgical patients despite early mobilisation being an important factor to enhance recovery. We therefore investigated possible effects of mobilisation on post-operative pain and nociceptive function after total knee arthroplasty (TKA). METHODS: Thirty patients undergoing TKA under standardised anaesthesia and analgesia underwent an exercise (mobilisation) strategy on the first post-operative morning consisting of 25-m walking twice, with a 20-min interval. Pain was assessed at rest and during passive hip and knee flexion before, and 5 and 20 min after walk, as well as during walk. Nociceptive function (pain threshold and tolerance) was assessed with pressure algometry and an electrical stimulus. RESULTS: Pain at rest (supine) and during hip and knee flexion was significantly reduced 5 min (P < 0.03) and 20 min (P < 0.003) after walk compared with before walk, and pain was reduced during the second walk compared with the first walk (P < 0.034). Knee pain pressure threshold (P = 0.002) but not tolerance (P = 0.27) was increased following walk compared with before walk. CONCLUSION: This first exploratory hypothesis-generating pilot study suggests mobilisation to promote analgesic effects after TKA calling for future studies with a randomised, controlled design on exercise dose-response effects in post-surgical patients.

Post-anaesthesia care unit stay after total hip and knee arthroplasty under spinal anaesthesia.

BACKGROUND: Post-anaesthesia care unit (PACU) admission must be well founded and the stay as short as possible without compromising patient safety. However, within the concept of fast-track surgery, studies are limited in addressing the question: why are patients staying in the PACU? METHODS: All patients operated with primary unilateral total hip or knee arthroplasty (THA or TKA) under spinal anaesthesia were included in this hypothesis-generating, prospective, observational cohort study during a 4-month period. Surgical technique, analgesia, and perioperative care were standardized. Well-defined PACU discharge criteria that had to be met on two successive assessments were evaluated every 15 min until discharge. The primary outcome was time to meet PACU discharge criteria. Secondary outcomes were actual discharge time from the PACU, specific factors detaining patients in the PACU, and potential complications at the surgical ward at follow-up 24 h post-operatively. RESULTS: One hundred sixty-three patients were included in the final analysis (69 THA and 94 TKA). Time to meet PACU discharge criteria was [median (interquartile range)(95% confidence interval)]: 15 min (15-15)(15-116) for THA and 15 min (15-15)(15-75) for TKA. Actual discharge time from PACU was: 25 min (20-35)(16-198) for THA and 25 min (20-31)(15-107) for TKA. Reasons for not meeting PACU discharge criteria in 15 min were mainly low oxygen saturation and pain. The short stay in the PACU did not impose complications at the surgical ward. CONCLUSION: The vast majority of patients (> 85%) operated with THA and TKA under low-dose spinal anaesthesia may achieve pre-defined PACU discharge criteria in 15 min. Large-scale studies should be performed to evaluate safety aspects after short PACU stay.

Effect of high-dose preoperative methylprednisolone on pain and recovery after total knee arthroplasty: a randomized, placebo-controlled trial.

BACKGROUND: Total knee arthroplasty (TKA) is associated with severe pain and inflammation despite an extensive multimodal analgesic approach, but the effect of high-dose glucocorticoid administration has not been studied. METHODS: Forty-eight patients undergoing unilateral TKA were included in a randomized, double-blind, placebo-controlled trial receiving preoperative methylprednisolone (MP) 125 mg i.v. or saline. All surgery was performed under lumbar spinal anaesthesia and patients received a standardized, multimodal analgesic regime. The primary endpoint was pain during walking 24 h after surgery, and secondary endpoints were pain at rest, pain upon hip flexion, and pain upon knee flexion. Pain assessments were performed repeatedly for the first 48 h after surgery, in a questionnaire from days 2 to 10, and at follow-up on days 21 and 30. Tertiary endpoints were postoperative nausea and vomiting (PONV), plasma C-reactive protein (CRP) concentrations, fatigue, sleep quality, and rescue analgesic and antiemetic requirements. RESULTS: Pain during walking was significantly lower in the MP group up to 32 h after operation. Overall pain and cumulative pain scores (2-48 h) were lower for all pain assessments (P<0.04). Consumption of rescue oxycodone was lower from 0 to 24 h (P=0.02) and PONV, consumption of ondansetron reduced (P<0.05), and CRP concentrations were lower at 24 h (P<0.000001). Fatigue throughout the day of surgery was lower (P=0.02), but sleep quality was worse on the first night (P=0.002). No side-effects or complications were observed in other respects. CONCLUSIONS: MP 125 mg before surgery improves analgesia and immediate recovery after TKA, even when combined with a multimodal analgesic regime. These findings call for further studies on safety aspects.