Pregabalin has demonstrated anti-hyperalgesic properties and was introduced into acute pain treatment in 2001. Our aim was to evaluate the beneficial and harmful effects of pregabalin in ...postoperative pain management. We included randomized clinical trials investigating perioperative pregabalin treatment in adult surgical patients. The review followed Cochrane methodology, including Grading of Recommendations Assessment, Development, and Evaluation (GRADE), and used trial sequential analyses (TSAs). The primary outcomes were 24 h morphine i.v. consumption and the incidence of serious adverse events (SAEs) defined by International Conference of Harmonisation Good Clinical Practice guidelines. Conclusions were based primarily on trials with low risk of bias. Ninety-seven randomized clinical trials with 7201 patients were included. The 24 h morphine i.v. consumption was reported in 11 trials with overall low risk of bias, finding a reduction of 5.8 mg (3.2, 8.5; TSA adjusted confidence interval: 3.2, 8.5). Incidence of SAEs was reported in 21 trials, with 55 SAEs reported in 12 of these trials, and 22 SAEs reported in 10 trials with overall low risk of bias. In trials with overall low risk of bias, Peto's odds ratio was 2.9 (1.2, 6.8; TSA adjusted confidence interval: 0.1, 97.1). Based on trials with low risk of bias, pregabalin may have a minimal opioid-sparing effect, but the risk of SAEs seems increased. However, the GRADE-rated evaluations showed only moderate to very low quality of evidence. Consequently, a routine use of pregabalin for postoperative pain treatment cannot be recommended.
The transversus abdominis plane (TAP) block is a newly described peripheral block involving the nerves of the anterior abdominal wall. The block has been developed for post‐operative pain control ...after gynaecologic and abdominal surgery. The initial technique described the lumbar triangle of Petit as the landmark used to access the TAP in order to facilitate the deposition of local anaesthetic solution in the neurovascular plane. Other techniques include ultrasound‐guided access to the neurovascular plane via the mid‐axillary line between the iliac crest and the costal margin, and a subcostal access termed the ‘oblique subcostal’ access. A systematic search of the literature identified a total of seven randomized clinical trials investigating the effect of TAP block on post‐operative pain, including a total of 364 patients, of whom 180 received TAP blockade. The surgical procedures included large bowel resection with a midline abdominal incision, caesarean delivery via the Pfannenstiel incision, abdominal hysterectomy via a transverse lower abdominal wall incision, open appendectomy and laparoscopic cholecystectomy. Overall, the results are encouraging and most studies have demonstrated clinically significant reductions of post‐operative opioid requirements and pain, as well as some effects on opioid‐related side effects (sedation and post‐operative nausea and vomiting). Further studies are warranted to support the findings of the primary published trials and to establish general recommendations for the use of a TAP block.
Post‐operative pain affects millions of patients worldwide and the post‐operative period has high rates of morbidity and mortality. Some of this morbidity may be related to analgesics. The aim of ...this review was to provide an update of current knowledge of adverse events (AE) associated with the most common perioperative non‐opioid analgesics: paracetamol, non‐steroidal anti‐inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta‐analyses of analgesic efficacy and/or adverse effects of perioperative non‐opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post‐operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality, cardiovascular events, surgical bleeding and renal impairment. Anastomotic leakage may be associated with NSAID usage. No firm evidence exists for an association of NSAIDs with impaired bone healing. Single‐dose GCCs were not significantly related to increased infection rates or delayed wound healing. Gabapentinoid treatment was associated with increased sedation, dizziness and visual disturbances, but the clinical relevance needs clarification. Importantly, data on AEs of combinations of the above analgesics are sparse and inconclusive. Despite the potential adverse events associated with the most commonly applied non‐opioid analgesics, including their combinations, reporting of such events is sparse and confined to the immediate perioperative period. Knowledge of benefit and harm related to multimodal pain treatment is deficient and needs clarification in large trials with prolonged observation.
Background
Total knee arthroplasty (TKA) is associated with intense post‐operative pain. Besides providing optimal analgesia, reduction in side effects and enhanced mobilization are important in this ...elderly population. The adductor‐canal‐blockade is theoretically an almost pure sensory blockade. We hypothesized that the adductor‐canal‐blockade may reduce morphine consumption (primary endpoint), improve pain relief, enhance early ambulation ability, and reduce side effects (secondary endpoints) after TKA compared with placebo.
Methods
Patients aged 50–85 years scheduled for TKA were included in this parallel double‐blind, placebo‐controlled randomized trial. The patients were allocated to receive a continuous adductor‐canal‐blockade with intermittent boluses via a catheter with either ropivacaine 0.75% (n = 34) or placebo (n = 37) (http://www.clinicaltrials.gov Identifier: NCT01104883).
Results
Seventy‐five patients were randomized in a 1 : 1 ratio and 71 patients were analyzed. Morphine consumption from 0 to 24 h was significantly reduced in the ropivacaine group compared with the placebo group (40 ± 21 vs. 56 ± 26 mg, P = 0.006). Pain was significantly reduced in the ropivacaine group during 45 degrees flexion of the knee (P = 0.01), but not at rest (P = 0.06). Patients in the ropivacaine group performed the ambulation test, the Timed‐Up‐and‐Go (TUG) test, at 24 h significantly faster than patients in the placebo group (36 ± 17 vs. 50 ± 29 s, P = 0.03).
Conclusion
The adductor‐canal‐blockade significantly reduced morphine consumption and pain during 45 degrees flexion of the knee compared with placebo. In addition, the adductor‐canal‐blockade significantly enhanced ambulation ability assessed by the TUG test.
In contemporary post‐operative pain management, patients are most often treated with combinations of non‐opioid analgesics, to enhance pain relief and to reduce opioid requirements and opioid‐related ...adverse effects. A diversity of combinations is currently employed in clinical practice, and no well‐documented ‘gold standards’ exist. The aim of the present topical, narrative review is to provide an update of the evidence for post‐operative analgesic efficacy with the most commonly used, systemic non‐opioid drugs, paracetamol, non‐steroidal anti‐inflammatory drugs (NSAIDs)/COX‐2 antagonists, glucocorticoids, gabapentinoids, and combinations of these. The review is based on data from previous systematic reviews with meta‐analyses, investigating effects of non‐opioid analgesics on pain, opioid‐requirements, and opioid‐related adverse effects. Paracetamol, NSAIDs, COX‐2 antagonists, and gabapentin reduced 24 h post‐operative morphine requirements with 6.3 (95% confidence interval: 3.7 to 9.0) mg, 10.2 (8.7, 11.7) mg, 10.9 (9.1, 12.8) mg, and ≥ 13 mg, respectively, when administered as monotherapy. The opioid‐sparing effect of glucocorticoids was less convincing, 2.33 (0.26, 4.39) mg morphine/24 h. Trials of pregabalin > 300 mg/day indicated a morphine‐sparing effect of 13.4 (4, 22.8) mg morphine/24 h. Notably, though, the available evidence for additive or synergistic effects of most combination regimens was sparse or lacking. Paracetamol, NSAIDs, selective COX‐2 antagonists, and gabapentin all seem to have well‐documented, clinically relevant analgesic properties. The analgesic effects of glucocorticoids and pregabalin await further clarification. Combination regimens are sparsely documented and should be further investigated in future studies.
Background:
In this proof‐of‐concept study, we investigated the effect of the predominantly sensory adductor‐canal‐blockade on established pain in the early post‐operative period after total knee ...arthroplasty (TKA). We hypothesised that the adductor‐canal‐blockade would reduce pain during flexion of the knee (primary end point) and at rest, as well as reducing morphine consumption and morphine‐related side effects (secondary outcomes) compared with placebo.
Methods:
We enrolled patients scheduled for elective TKA into this double‐blind, placebo‐controlled, randomised study. During general anaesthesia, we placed a catheter in the adductor canal, and after obtaining pre‐block pain scores 30 min post‐operatively, we injected 30 ml of ropivacaine 0.75% (n = 21) or saline (n = 20) according to randomisation. Clinicaltrials.gov Identifier: NCT01261897.
Results:
Forty‐two patients were randomised, and 41 were analysed. Mean (standard deviation) pain scores during flexion of the knee at 1 h post‐operatively were 58 (22) mm and 67 (29) mm, ropivacaine and placebo group, respectively (P = 0.23) but was significantly reduced in the ropivacaine group when calculated as area under the curve for the interval 1–6 h (P = 0.02). There were no statistically significant differences regarding pain at rest (P = 0.08), morphine consumption (P = 0.06), nor morphine‐related side effects, apart from nausea (P = 0.04).
Conclusion:
This proof‐of‐concept study shows promising results regarding the analgesic efficacy of adductor‐canal‐blockade in post‐operative pain treatment after TKA, with a significant reduction in pain during flexion of the knee in the early post‐operative period compared with placebo. However, the study was not sufficiently powered to permit final conclusions.
Background
Rehabilitation efforts after treatment in the intensive care unit (ICU) are termed intensive care aftercare. It includes both early in‐hospital follow‐up after ICU‐discharge and late ...follow‐up after hospital discharge. This study aims to investigate the current ICU‐aftercare activities in Denmark.
Methods
We conducted an electronic questionnaire survey, which was distributed by e‐mail to the heads of all 31 general ICUs in Denmark. Specialized ICUs were not included. The questionnaire was divided into the following sections: early ICU‐aftercare, late ICU‐aftercare, future development and demographics.
Results
Thirty‐one ICUs were invited to participate. The response rate was 100%. Overall, 26 of 31 ICUs (84%) offered ICU‐aftercare, with the following distribution: early ICU‐aftercare (58%), late ICU‐aftercare (57%) and both (29%). There were no significant associations between hospital size and provision of ICU‐aftercare. For early ICU‐aftercare, the most common eligibility criteria were based on ICU length of stay (LOS) (44%) and a decision based upon doctors' discretion (22%). Incidence of guidelines for early ICU‐aftercare (44%) and checklists at patient contact (35%) were sparse. The most common early ICU‐aftercare items were as follows: respiratory care (82%), tracheostomy care (59%) and nutritional care (59%). For late ICU‐aftercare, the most common eligibility criterion was LOS (41%). Guidelines (71%), but not checklist at patient contact (35%), were more common. Most frequent late ICU‐aftercare interventions were review of ICU‐diaries (59%) and patient charts (53%).
Conclusion
Eighty‐four per cent of Danish ICUs offered ICU‐aftercare to their patients. There was an abundant heterogeneity of eligibility criteria and ICU‐aftercare interventions.
Background
Perioperative pain treatment often consist of combinations of non‐opioid and opioid analgesics, ‘multimodal analgesia’, in which gabapentin is currently used. The aim was to document ...beneficial and harmful effects of perioperative gabapentin treatment.
Methods
Randomized clinical trials comparing gabapentin vs. placebo or active placebo in adult surgical patients receiving gabapentin perioperatively were included. This review was conducted using Cochrane standards, trial sequential analysis (TSA), and Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The primary outcomes were 24‐h opioid consumption and incidence of serious adverse events (SAE).
Results
One hundred and thirty‐two trials with 9498 patients were included. Thirteen trials with low risk of bias reported a reduction in 24‐h opioid consumption of 3.1 mg 0.5, 5.6; TSA‐adjusted CI: −0.2, 6.3. In the analysis of gabapentin as add‐on analgesic to another non‐opioid analgesic regimen, a mean reduction in 24‐h morphine consumption of 1.2 mg −0.3, 2.6; TSA‐adjusted CI: −0.4, 2.8 in trials with low risk of bias was found. Nine trials with low risk of bias reported a risk ratio of SAEs of 1.61 0.91; 2.86; TSA‐adjusted CI: 0.57, 4.57.
Conclusion
Based on GRADE assessment of the primary outcomes in trials with low risk of bias, the results are low or very low quality of evidence due to imprecision, inconsistency, and in some outcomes indirectness. Firm evidence for use of gabapentin is lacking as clinically relevant beneficial effect of gabapentin may be absent and harm is imminent, especially when added to multimodal analgesia.
Total knee arthroplasty (TKA) is associated with varying degrees of pain. A considerable proportion (25–40%) of patients experience severe pain, despite a comprehensive multimodal analgesic regimen. ...We hypothesized that adductor canal block (ACB) would reduce pain in this patient category compared with placebo.
Fifty patients with severe pain, defined as having a visual analogue scale (VAS) pain score of >60 during active flexion of the knee on the first or the second postoperative day after TKA, were included in this randomized, double-blind, placebo-controlled trial. All the patients had received a comprehensive multimodal analgesic regimen. Group A received an ACB with ropivacaine 0.75%, 30 ml at time 0 and isotonic saline after 45 min. Group B received an ACB with isotonic saline at time 0 and ropivacaine 0.75%, 30 ml after 45 min.
A 32-mm difference in VAS pain score, during active flexion of the knee (primary endpoint), was observed in favour of Group A, 95% confidence interval (CI): 23–42, P<0.0001. At rest, the difference in VAS pain score was 15 mm in favour of Group A, 95% CI: 8–23 mm, P=0.0001. Individual patient analysis revealed that 25% of the patients had no effect during active flexion. At rest, however, only 8% had more than mild pain after ACB compared with 57% at inclusion.
ACB reduced VAS with 32 mm, during active flexion of the knee, in patients with severe pain after TKA, but a large proportion (78%) still had at least moderate, movement-related pain.
www.clinicaltrials.gov, NCT01549704.
Summary
It is difficult to pool results from randomised clinical trials that report different outcomes. We want to develop a core set of pain‐related outcomes after total hip or knee arthroplasty, ...the first stage of which is to systematically review published outcomes. We searched PubMed, Embase and CENTRAL for relevant trials to January 2020. We identified 165 outcomes from 565 trials with 50,668 participants, which we categorised into six domains: pain; analgesic consumption; quality of care; adverse events; mobility; and patient‐reported outcome measures. The outcome in each domain reported by most trials was: visual analogue score for pain, 401 (71%); morphine consumption, 212 (38%); length of hospital stay, 166 (29%); nausea or vomiting, 425 (75%); range of motion, 173 (31%); and patient satisfaction score, 181 (32%). A primary outcome was reported in 281 (50%) trials: 101 (18%) trials reported consumption of rescue analgesics and 95 (17%) trials reported pain. We plan to publish a consensus on outcomes that should be reported in postoperative pain trials after hip or knee arthroplasty.
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