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.
Intense pain can last several days after tonsillectomy. It is often undertreated and improved analgesic strategies that can be safely used at home are needed.
We conducted a systematic review and ...meta-analysis on the effectiveness of systemic medications used for post-tonsillectomy pain in adult and adolescent (13 yr old) patients. Studies were identified from PubMed, the Cochrane Library, and by hand searching reference lists from studies and review articles. Randomised, double-blind, placebo-controlled studies reporting on pain intensity or use of rescue analgesia were included.
Twenty-nine randomised controlled trials representing 1816 subjects met the inclusion criteria. Follow-up time was ≤24 h in 15 studies, in which the majority were taking nonsteroidal anti-inflammatory drugs. Thirteen studies were suitable for meta-analysis. In pooled analysis, paracetamol, dexamethasone, and gabapentinoids reduced pain intensity on the day of operation. In individual studies, ketoprofen, ibuprofen, lornoxicam, parecoxib, rofecoxib, indomethacin and dextromethorphan reduced pain intensity, need for rescue analgesics, or both on the day of operation. Oral celecoxib for 2 postoperative weeks or i.v. ketamine on the day of operation were not effective at the studied doses. Dexamethasone in multiple doses provided analgesia beyond 1 postoperative day. Pain was moderate to strong in both study and control groups during the first postoperative week.
Single analgesics and dexamethasone provide only a weak to moderate effect for post-tonsillectomy pain on the day of operation and thus a multimodal analgesic strategy is recommended. Short follow-up times and clinical heterogeneity of studies limit the usefulness of results.
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.
Aim: Defined daily dose (DDD) is the most common measurement unit used in drug consumption studies. The DDD for opioids may not reflect their relative clinical potencies. The aim of this study was to ...explore whether opioid consumption data may be interpreted differently when adding oral morphine equivalent (OMEQ) dose as a measurement unit compared with using DDD.
Methods: The equianalgesic ratio of each opioid relative to morphine was tabulated. Data on opioid consumption expressed in DDD were converted to OMEQs using the equianalgesic ratios. The opioid consumption was compared in three different study settings: clinical data from an opioid switching study, trends within one country and a comparison between countries.
Results: Using DDD, the opioid consumption in Norway between 2004–2008 increased of 6.7%, while the increase was 23.6% using OMEQ. While DDD/1000 inhabitants/day showed that Sweden had the highest consumption of opioids among the Nordic countries, OMEQ/1000 inhabitants/day showed that Denmark had the highest consumption. In the switching study DDD indicated a reduction in analgesic dosing and OMEQ an increase when switching from WHO step II to III.
Conclusion: OMEQ reflects clinical dosing better than DDD, and can give additional insight into opioid consumption when combined with DDD. Using OMEQ can also lead to different conclusions in opioid consumption studies compared with using DDD alone.
Photoplethysmographic pulse wave amplitude (PPGA) and heart rate (HR) can be used to measure cold, nociception-induced autonomic responses, or both. The aim of our study was to correlate the ...intensity of experimental pain to changes in physiological variables reflecting the autonomic nervous system response to pain.
PPGA, HR, and subjective measurements of pain intensity were measured in 29 healthy male volunteers during two heat stimuli (43°C and 48°C) and the cold pressor test (CPT). Surgical pleth index (SPI), autonomic nervous system state (ANSS), and ANSS index (ANSSi) were calculated using PPGA and HR.
Pain intensity scores increased on the average by 1.6, 3.5, and 8.1 for the 43°C, 48°C, and CPT stimuli, respectively. The pain intensity scores for all three stimuli groups were significantly different from each other (P<0.001). All three stimuli changed HR, PPGA, SPI, ANSS, and ANSSi values significantly from their respective baseline values (P<0.001 for all). Heat stimuli-induced pain intensity did not correlate with the magnitude of the respective changes in HR, PPGA, SPI, ANSS, and ANSSi. CPT-induced pain intensity correlated with the magnitude of the respective changes in HR, PPGA, SPI, ANSS, and ANSSi. PPGA, ANSSi, ANSS, and SPI differentiated between heat and cold stimuli-induced pain.
All three thermal stimuli produced a significant change in photoplethysmograph-derived parameters. All photoplethysmograph-derived parameters appear to be suitable to study autonomic nervous system activation.
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.
In this systematic review effectiveness of analgesics for pain after tonsillectomy in children was evaluated and trial methodology of the included studies explored. Databases were searched for ...randomised, controlled studies on systemic paracetamol, NSAIDs and opioids. Eighty-four studies were evaluated for inclusion. Thirty-six studies were included and 48 excluded. Only in two studies investigated analgesics were given postoperatively for pain. All other studies investigated prophylactic administration of analgesics. Only five studies were truly placebo controlled. Trial methodology of the included studies varied greatly in respect to analgesics and doses used, duration of follow-up periods, methods of pain measurement, rescue analgesics and criteria for administrating rescue analgesia used. Sensitivity of studies was often unclear. Only 16 out of 36 studies were considered to be sensitive. Because of highly variable methodology and lack of sensitivity only limited conclusions on clinical efficacy of analgesics investigated can be drawn. No analgesic in single prophylactic dose provided analgesia for day of operation. Further studies are needed to find the optimal analgesic(s) for pain after tonsillectomy in children.
Abstract Aims The aim of the study was to describe the clinical features and clinical pathway of pediatric CRPS patients in HUH Children’s Hospital. Methods This retrospective study included patients ...admitted to the pediatric pain clinic for CRPS during six years 2008-2013. Data on time from the first symptoms to diagnosis, first appointment at the pain clinic, and symptom resolution, as well as demographic and clinical symptoms were extracted from patient records. Results Forty patients were clinically diagnosed with CRPS during the time period without using the Budapest Criteria. 75% of the patients were female, median age was 12, and in 90% of the cases the CRPS was localized in the lower extremity. The median time from first symptoms to the CRPS diagnosis was 8.5 weeks (range 0-47), to first appointment with the pain physician 10 weeks (range 2-47), and to symptom resolution 35 weeks (range 10-131). Eleven out of forty patients (27.5%) were not symptom-free at the end of the treatment period. Most common clinical finding was allodynia or hyperalgesia of the afflicted area (70%). Conclusions Compared to an earlier study performed in our hospital (retrospective study of seven years, n = 18), the number of patients has more than doubled, maybe due to better awareness of the syndrome. Our findings about demographics and localization of CRPS are in agreement with previous literature. Time to reaching diagnosis, the small number of consultations and radiographs show that CRPS is well known among pediatric orthopedic surgeons. Many Budapest criteria that are now considered important diagnostic findings were not highly prevalent in our patients (e.g. prior trauma, color changes of skin), although patient records were not always clear about the findings leading to diagnosis. The Budapest criteria should be used to standardize the diagnosis also in our pediatric patients.
Gabapentin and pregabalin have antiallodynic and antihyperalgesic properties useful for treating neuropathic pain. These properties may also be beneficial in acute postoperative pain. In this study ...we evaluated randomized, controlled trials examining the analgesic efficacy, adverse effects, and clinical value of gabapentinoids in postoperative pain.
A systematic search of Medline, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL) databases yielded 22 randomized, controlled trials on perioperative administration of gabapentinoids for postoperative pain relief.
Pain relief was better in the gabapentin groups compared with the control groups. The opioid-sparing effect during the first 24 h after a single dose of gabapentin 300-1200 mg, administered 1-2 h preoperatively, ranged from 20% to 62%. The combined effect of a single dose of gabapentin was a reduction of opioid consumption equivalent to 30 +/- 4 mg of morphine (mean +/- 95% CI) during the first 24 h after surgery. Metaregression analysis suggested that the gabapentin-induced reduction in the 24-h opioid consumption was not significantly dependent on the gabapentin dose. Gabapentin reduced opioid-related adverse effects, such as nausea, vomiting, and urinary retention (number-needed-to-treat 25, 6, and 7, respectively). The most common adverse effects of the gabapentinoids were sedation and dizziness (number-needed-to-harm 35 and 12, respectively).
Gabapentinoids effectively reduce postoperative pain, opioid consumption, and opioid-related adverse effects after surgery. Conclusions about the optimal dose and duration of the treatment cannot be made because of the heterogeneity of the trials. Studies are needed to determine the long-term benefits, if any, of perioperative gabapentinoids.
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