Associations of dexamethasone's effect on morphine consumption after total knee arthroplasty-Subgroup analyses.

The DEXamethasone twice for pain treatment after Total Knee Arthroplasty (DEX-2-TKA) trial showed that adding one and two doses of 24 mg intravenous dexamethasone to paracetamol, ibuprofen and local infiltration analgesia, reduced morphine consumption (primary outcome) within 48 h after TKA. We aimed to explore the differences in the effect of dexamethasone on morphine consumption in different subgroups. Quantile regression adjusted for site was used to test for significant interaction between the predefined dichotomised subgroups and treatment group. The subgroups were defined based on baseline data: sex (male/female), age (≤65 years/>65 years), American Society of Anaesthesiologists (ASA)-score (ASA I + II/III), visual analogue score of preoperative pain at rest (≤30 mm/>30 mm), pain during mobilisation (≤30 mm/>30 mm), type of anaesthesia (spinal anaesthesia/general anaesthesia and spinal converted to general anaesthesia), and prior daily use of analgesics (either paracetamol and/or NSAID/neither). These analyses were supplemented with post hoc multivariate linear regression analyses. Test of interaction comparing sex in the pairwise comparison between DX2 (dexamethasone [24 mg] + dexamethasone [24 mg]) versus placebo (p = .02), showed a larger effect of dexamethasone on morphine consumption in male patients compared to females. Test of interaction comparing age in the pairwise comparison between DX1 (dexamethasone [24 mg] + placebo) versus placebo (p = .04), showed a larger effect of dexamethasone on morphine consumption in younger patients (≤65 years) compared to older. All remaining subgroup analyses showed no evidence of a difference. The supplemental multivariate analyses did not support any significant interaction for sex (p = .256) or age (p = .730) but supported a significant interaction with the type of anaesthesia (p < .001). Our results from the quantile regression analyses indicate that the male sex and younger age (≤65 years) may be associated with a larger analgesic effect of dexamethasone than the effects in other types of patients. However, this is not supported by post-hoc multivariate linear regression analyses. The two types of analyses both supported a possible interaction with the type of anaesthesia.

DEX-2-TKA-DEXamethasone twice for pain treatment after Total Knee Arthroplasty: A protocol for a randomized, blinded, three-group multicentre clinical trial.

BACKGROUND: Multimodal analgesia is considered the leading principle for post-operative pain treatment, but no gold standard after total knee arthroplasty (TKA) exists. AIM: To investigate the beneficial and harmful effects of one or two doses of 24 mg intravenous dexamethasone (DXM) as part of a multimodal analgesic regimen (paracetamol, NSAID and perioperative local infiltration analgesia) after TKA. We hypothesize that addition of DXM will reduce post-operative opioid consumption. METHODS: DEXamethasone twice for pain treatment after TKA is a randomized, blinded, three-group multicentre clinical trial. Participants will be randomized to one of three groups: placebo, single dose of DXM or two consecutive doses of DXM. Participants, treatment providers and investigators will be blinded to the allocated intervention. The primary outcome is total opioid consumption (units of morphine equivalents) 0-48 hours post-operatively. INCLUSION CRITERIA: unilateral, primary TKA; age ≥18 years; American Society of Anesthesiologists-Score 1-3; Body Mass Index ≥18 and ≤40; for women-not pregnant; and written informed consent. EXCLUSION CRITERIA: allergy or contraindications against trial medication; daily use of high dose opioid and/or use of methadone/transdermal opioids; daily use of systemic glucocorticoids; dysregulated diabetes; and patients suffering from alcohol and/or drug abuse. Four-hundred-and-eighty-six eligible participants are needed to detect or discard a difference of 10 mg morphine equivalents 0-48 hours post-operatively maintaining a familywise error rate of 0.05 and a power of 90% for the three possible pairwise comparisons. DISCUSSION: Recruiting is planned to commence September 2018 and expected to finish March 2020. TRIAL REGISTRATION: EudraCT: 2018-001099-39 (08/06-18); ClinicalTrials.gov: NCT03506789 (24/04-2019). Editorial Comment This is the protocol for the largest randomized clinical trial investigating the effect of one or two doses of dexamethasones on pain treatment after total knee arthroplasty. Due to the pragmatic and rigerous design this study will deliver results of high quality and external validity.

Self-positioning followed by induction of anaesthesia and insertion of a laryngeal mask airway versus endotracheal intubation and subsequent positioning for spinal surgery in the prone position: a randomised clinical trial.

BACKGROUND: Anaesthesia followed by positioning in the prone position takes time and may have complications. OBJECTIVE: The hypothesis was that self-positioning in the prone position followed by anaesthesia and introduction of a laryngeal mask airway (LM method) would be faster with fewer complications than positioning after tracheal intubation (ET method). DESIGN: Randomised, controlled trial. SETTING: University Hospital, March 2009 to March 2011. PATIENTS: One hundred forty patients scheduled for spinal surgery were allocated to the LM or the ET method. Exclusion criteria were surgery expected to last more than 2 h, American Society of Anesthesiologists status more than II, age more than 70 years, abnormal neck, throat, and mouth anatomy and function, Mallampati score III-IV, BMI more than 35 kg m, anticipated difficult airway/mask ventilation and decreased neck mobility. INTERVENTIONS: Patients in the LM group placed themselves in the prone position, anaesthesia was induced and a laryngeal mask was introduced. Patients in the ET group were anaesthetised, intubated and then placed in the prone position. MAIN OUTCOME MEASURES: Time taken from identification of the patient at the outset to readiness for radiographic examination following anaesthesia and positioning. Airway problems, sore throat, hoarseness and pain from muscles and joints were also noted. RESULTS: One hundred and forty patients were randomised to LM (n = 70) and ET (n = 70). Data from 64 and 67 patients were analysed. Values are expressed as median (interquartiles) [range]. The primary outcome time was 25 min (23 to 29) [16 to 44] in the LM group and 30 min (26 to 33) [17 to 47] in the ET group (P <0.001). In two patients in group LM, a complete seal could not be obtained; one was intubated, and the other had surgery cancelled due to arterial hypotension. There were fewer cases with sore throat, hoarseness and pain from muscles and joints in the LM group at 3 h, but not at 24 h postoperatively. CONCLUSION: Self-positioning and induction of anaesthesia in the prone position saves time. More patients should be studied to confirm safety and examine whether the method reduces the number of severe complications associated with the prone position. TRIAL REGISTRATION: www.clinicaltrials.gov identifier: NCT01041352.

A randomized, controlled trial comparing local infiltration analgesia with epidural infusion for total knee arthroplasty.

BACKGROUND: There have been few studies describing wound infiltration with additional intraarticular administration of multimodal analgesia for total knee arthroplasty (TKA). In this study, we assessed the efficacy of wound infiltration combined with intraarticular regional analgesia with epidural infusion on analgesic requirements and postoperative pain after TKA. METHODS: 40 consecutive patients undergoing elective, primary TKA were randomized into 2 groups to receive either (1) intraoperative wound infiltration with 150 mL ropivacaine (2 mg/mL), 1 mL ketorolac (30 mg/mL), and 0.5 mL epinephrine (1 mg/mL) (total volume 152 mL) combined with intraarticular infusion (4 mL/h) of 190 mL ropivacaine (2 mg/mL) plus 2 mL ketorolac (30 mg/mL) (group A), or (2) epidural infusion (4 mL/h) of 192 mL ropivacaine (2 mg/mL) combined with 6 intravenous administrations of 0.5 mL ketorolac (30 mg/mL) for 48 h postoperatively (group E). For rescue analgesia, intravenous patient-controlled-analgesia (PCA) morphine was used. Morphine consumption, intensity of knee pain (0­100 mm visual analog scale), and side effects were recorded. Length of stay and corrected length of stay were also recorded (the day-patients fulfilled discharge criteria). RESULTS: The median cumulated morphine consumption, pain scores at rest, and pain scores during mobilization were reduced in group A compared to group E. Corrected length of stay was reduced by 25% in group A compared to group E. INTERPRETATION: Peri- and intraarticular analgesia with multimodal drugs provided superior pain relief and reduced morphine consumption compared with continuous epidural infusion with ropivacaine combined with intravenous ketorolac after TKA.