Ketamine analgo-sedation for mechanically ventilated critically ill adults: A rapid practice guideline from the Saudi Critical Care Society and the Scandinavian Society of Anesthesiology and Intensive Care Medicine.

BACKGROUND: This Rapid Practice Guideline (RPG) aimed to provide evidence-based recommendations for ketamine analgo-sedation (monotherapy and adjunct) versus non-ketamine sedatives or usual care in adult intensive care unit (ICU) patients on invasive mechanical ventilation (iMV) and to identify knowledge gaps for future research. METHODS: The RPG panel comprised 23 multinational multidisciplinary panelists, including a patient representative. An up-to-date systematic review and meta-analysis constituted the evidence base. The Grading Recommendations, Assessment, Development, and Evaluation approach, and the evidence-to-decision framework were used to assess the certainty of evidence and to move from evidence to decision/recommendation. The panel provided input on the balance of the desirable and undesirable effects, certainty of evidence, patients' values and preferences, costs, resources, equity, feasibility, acceptability, and research priorities. RESULTS: Data from 17 randomized clinical trials (n = 898) and nine observational studies (n = 1934) were included. There was considerable uncertainty about the desirable and undesirable effects of ketamine monotherapy for analgo-sedation. The evidence was very low certainty and downgraded for risk of bias, indirectness, and inconsistency. Uncertainty or variability in values and preferences were identified. Costs, resources, equity, and acceptability were considered varied. Adjunctive ketamine therapy had no effect on mortality (within 28 days) (relative risk [RR] 0.99; 95% confidence interval [CI] 0.76 to 1.27; low certainty), and may slightly reduce iMV duration (days) (mean difference [MD] -0.05 days; 95% CI -0.07 to -0.03; low certainty), and uncertain effect on the cumulative dose of opioids (mcg/kg/h morphine equivalent) (MD -11.6; 95% CI -20.4 to -2.7; very low certainty). Uncertain desirable effects (cumulative dose of sedatives and vasopressors) and undesirable effects (adverse event rate, delirium, arrhythmia, hepatotoxicity, hypersalivation, use of physical restraints) were also identified. A possibility of important uncertainty or variability in patient-important outcomes led to a balanced effect that favored neither the intervention nor the comparison. Cost, resources, and equity were considered varied. CONCLUSION: The RPG panel provided two conditional recommendations and suggested (1) against using ketamine as monotherapy analgo-sedation in critically ill adults on iMV when other analgo-sedatives are available; and (2) using ketamine as an adjunct to non-ketamine usual care sedatives (e.g., opioids, propofol, dexmedetomidine) or continuing with non-ketamine usual care sedatives alone. Large-scale trials should provide additional evidence.

Ketamine Analgo-sedation for Mechanically Ventilated Critically Ill Adults: A Rapid Practice Guideline from the Saudi Critical Care Society and the Scandinavian Society of Anesthesiology and Intensive Care Medicine.

BACKGROUND: This Rapid Practice Guideline (RPG) aimed to provide evidence­based recommendations for ketamine analgo-sedation (monotherapy and adjunct) versus non-ketamine sedatives or usual care in adult intensive care unit (ICU) patients on invasive mechanical ventilation (iMV) and to identify knowledge gaps for future research. METHODS: The RPG panel comprised 23 multinational multidisciplinary panelists, including a patient representative. An up-to-date systematic review and meta-analysis constituted the evidence base. The Grading Recommendations, Assessment, Development, and Evaluation approach, and the evidence-to-decision framework were used to assess the certainty of evidence and to move from evidence to decision/recommendation. The panel provided input on the balance of the desirable and undesirable effects, certainty of evidence, patients' values and preferences, costs, resources, equity, feasibility, acceptability, and research priorities. RESULTS: Data from 17 randomized clinical trials (n=898) and 9 observational studies (n=1934) were included. There was considerable uncertainty about the desirable and undesirable effects of ketamine monotherapy for analgo-sedation. The evidence was very low certainty and downgraded for risk of bias, indirectness, and inconsistency. Uncertainty or variability in values and preferences were identified. Costs, resources, equity, and acceptability were considered varied. Adjunctive ketamine therapy had no effect on mortality (within 28 days) (relative risk [RR] 0.99; 95% confidence interval [CI] 0.76 to 1.27; low certainty), and may slightly reduce iMV duration (days) (mean difference [MD] -0.05 days; 95% CI -0.07 to -0.03; low certainty), and uncertain effect on the cumulative dose of opioids (mcg/kg/h morphine equivalent) (MD -11.6; 95% CI -20.4 to -2.7; very low certainty). Uncertain desirable effects (cumulative dose of sedatives and vasopressors) and undesirable effects (adverse event rate, delirium, arrhythmia, hepatotoxicity, hypersalivation, use of physical restraints) were also identified. A possibility of important uncertainty or variability in patient-important outcomes led to a balanced effect that favored neither the intervention nor the comparison. Cost, resources, and equity were considered varied. CONCLUSION: The RPG panel provided two conditional recommendations and suggested (1) against using ketamine as monotherapy analgo-sedation in critically ill adults on iMV when other analgo-sedatives are available; and (2) using ketamine as an adjunct to non-ketamine usual care sedatives (e.g., opioids, propofol, dexmedetomidine) or continuing with non-ketamine usual care sedatives alone. Large-scale trials should provide additional evidence.

ESAIC focused guideline for the use of cardiac biomarkers in perioperative risk evaluation: Endorsement by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

BACKGROUND: The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the clinical practice guideline "ESAIC focused guideline for the use of cardiac biomarkers in perioperative risk evaluation." The guideline can provide guidance to Nordic anaesthesiologists on the perioperative use of cardiac biomarkers in patients undergoing non-cardiac surgery.

Influence of Clinical and Genetic Factors on Propofol Dose Requirements: A Genome-wide Association Study.

BACKGROUND: Propofol is a widely used intravenous hypnotic. Dosing is based mostly on weight, with great interindividual variation in consumption. Suggested factors affecting propofol requirements include age, sex, ethnicity, anxiety, alcohol consumption, smoking, and concomitant valproate use. Genetic factors have not been widely explored. METHODS: This study considered 1,000 women undergoing breast cancer surgery under propofol and remifentanil anesthesia. Depth of anesthesia was monitored with State Entropy (GE Healthcare, Finland). Propofol requirements during surgery were recorded. DNA from blood was genotyped with a genome-wide array. A multivariable linear regression model was used to assess the relevance of clinical variables and select those to be used as covariates in a genome-wide association study. Imputed genotype data were used to explore selected loci further. In silico functional annotation was used to explore possible consequences of the discovered genetic variants. Additionally, previously reported genetic associations from candidate gene studies were tested. RESULTS: Body mass index, smoking status, alcohol use, remifentanil dose (ln[mg · kg-1 · min-1]), and average State Entropy during surgery remained statistically significant in the multivariable model. Two loci reached genome-wide significance (P < 5 × 10-8). The most significant associations were for single-nucleotide polymorphisms rs997989 (30 kb from ROBO3), likely affecting expression of another nearby gene, FEZ1, and rs9518419, close to NALCN (sodium leak channel); rs10512538 near KCNJ2 encoding the Kir2.1 potassium channel showed suggestive association (P = 4.7 × 10-7). None of these single-nucleotide polymorphisms are coding variants but possibly affect the regulation of nearby genes. None of the single-nucleotide polymorphisms previously reported as affecting propofol pharmacokinetics or pharmacodynamics showed association in the data. CONCLUSIONS: In this first genome-wide association study exploring propofol requirements, This study discovered novel genetic associations suggesting new biologically relevant pathways for propofol and general anesthesia. The roles of the gene products of ROBO3/FEZ1, NALCN, and KCNJ2 in propofol anesthesia warrant further studies.

Physiologically based pharmacokinetic modeling of ritonavir-oxycodone drug interactions and its implication for dosing strategy.

The concomitant administration of ritonavir and oxycodone may significantly increase the plasma concentrations of oxycodone. This study was aimed to simulate DDI between ritonavir and oxycodone, a widely used opioid, and to formulate dosing protocols for oxycodone by using physiologically based pharmacokinetic (PBPK) modeling. We developed a ritonavir PBPK model incorporating induction and competitive and time-dependent inhibition of CYP3A4 and competitive inhibition of CYP2D6. The ritonavir model was evaluated with observed clinical pharmacokinetic data and validated for its CYP3A4 inhibition potency. We then used the model to simulate drug interactions between oxycodone and ritonavir under various dosing scenarios. The developed model captured the pharmacokinetic characteristics of ritonavir from clinical studies. The model also accurately predicts exposure changes of midazolam, triazolam, and oxycodone in the presence of ritonavir. According to model simulations, the steady-state maximum, minimum and average concentrations of oxycodone increased by up to 166% after co-administration with ritonavir, and the total exposure increased by approximately 120%. To achieve similar steady-state concentrations, halving the dose with an unchanged dosing interval or doubling the dosing interval with an unaltered single dose should be practical for oxycodone, whether formulated in uncoated or controlled-release tablets during long-term co-medication with ritonavir. The results revealed exposure-related risks of oxycodone-ritonavir interactions that have not been studied clinically and emphasized PBPK as a workable method to direct judicious dosage.

Influence of Intravenous S-Ketamine on the Pharmacokinetics of Oral Morphine in Healthy Volunteers.

BACKGROUND: Subanesthetic ketamine may reduce perioperative consumption of opioids. We studied whether intravenous S-ketamine alters the pharmacokinetics of oral morphine in healthy volunteers. METHODS: In this paired, randomized, double-blind, crossover trial, 12 participants under a 2-hour intravenous S-ketamine (0.57 mg/kg/h) or placebo infusion received oral morphine (0.2 mg/kg) at 30 minutes. Plasma concentrations of ketamine, morphine, and their major metabolites were quantified for 24 hours. The primary end point was area under the curve (AUC) 0-24 of morphine. Other pharmacokinetic variables for morphine and its metabolites were studied as secondary end points. The data were analyzed as between-phase comparisons for each participant using Wilcoxon matched-pairs signed-rank tests ( tmax ) or paired t -tests on log-transformed variables (other variables). RESULTS: While the AUC 0-24 was similar between the 2 phases, S-ketamine reduced the AUC 0-1.5 of oral morphine by 69% (ratio to control, 0.31; 90% confidence interval [CI], 0.15-0.65; P = .0171) and increased its tmax from 0.5 (range, 0.50-1.5) to 1.0 hour (range, 0.50-4.0; P = .010). The AUC 0-1.5 of morphine-6-glucuronide (M6G) was reduced by 84% (0.16; 90% CI, 0.07-0.37; P = .0025) and maximum plasma concentration ( Cmax ) by 43% (0.57; 90% CI, 0.40-0.81; P = .0155), while its tmax was increased from 1.5 (range, 1.0-2.0) to 4.0 (range, 1.0-8.0; P = .0094) hours by S-ketamine. Similarly, the AUC 0-1.5 of morphine-3-glucuronide (M3G) was reduced by 85% (0.15; 90% CI, 0.05-0.43; P = .0083), and tmax increased from 1.0 (range, 0.5-1.5) to 4.0 hours (range, 1.0-8.0; P = .0063). In addition, the M6G-to-morphine and M3G-to-morphine metabolic AUC ratios were decreased by 47% (0.53; 90% CI, 0.39-0.71; P = .0033) and 52% (0.48; 90% CI, 0.27-0.85; P = .0043) during 0 to 1.5 hours and by 15% (0.85; 90% CI, 0.78-0.92; P = .0057) and 10% (0.90; 90% CI, 0.83-0.98; P = .0468) during 0 to 24 hours, respectively. One participant was excluded from the analyses due to vomiting in the S-ketamine phase. CONCLUSIONS: Intravenous S-ketamine inhibited the metabolism of oral morphine and delayed its absorption, resulting in a net reduction in the exposure to morphine during the first 1.5 hours. Intravenous S-ketamine may delay the absorption and impair the efficacy of orally administered analgesics and other drugs.

Awake proning in patients with COVID-19-related hypoxemic acute respiratory failure: Endorsement by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

BACKGROUND: Awake proning in spontaneously breathing patients with hypoxemic acute respiratory failure was applied during the coronavirus disease 2019 (COVID-19) pandemic to improve oxygenation while avoiding tracheal intubation. An updated systematic review and meta-analysis on the topic was published. METHODS: The Clinical practice committee (CPC) of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) assessed the clinical practice guideline "Awake proning in patients with COVID-19-related hypoxemic acute respiratory failure: A rapid practice guideline" for possible endorsement. The Appraisal of Guidelines for REsearch and Evaluation (AGREE) II tool was used. RESULTS: Four out of six SSAI CPC members completed the appraisal. The individual domain totals were: Scope and Purpose 90%; Stakeholder Involvement 89%; Rigour of Development 74%; Clarity of Presentation 85%; Applicability 75%; Editorial Independence 98%; Overall Assessment 79%. CONCLUSION: The SSAI CPC endorses the clinical practice guideline "Awake proning in patients with COVID-19-related hypoxemic acute respiratory failure: A rapid practice guideline". This guideline serves as a useful decision aid for clinicians caring for critically ill patients with COVID-19-related acute hypoxemic respiratory failure and can be used to provide guidance on use of prone positioning in this group of patients.

ISTH guidelines for antithrombotic treatment in COVID-19: Endorsement by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the ISTH guidelines for antithrombotic treatment in COVID-19. This evidence-based guideline serves as a useful decision aid for Nordic anaesthesiologists caring for patients with COVID-19.

Saudi Critical Care Society clinical practice guidelines on the prevention of venous thromboembolism in adults with trauma: Endorsement by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the clinical practice guideline Saudi Critical Care Society clinical practice guidelines on the prevention of venous thromboembolism in adults with trauma: reviewed for evidence-based integrity and endorsed by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine. This clinical practice guideline serves as a useful decision aid for Nordic anaesthesiologists managing adult trauma patients in the operating room and in the intensive care unit.

Testing of a predictive risk index for persistent postsurgical pain on patients undergoing total knee arthroplasty: A prospective cohort study.

BACKGROUND: We investigated whether a universal predictive risk index for persistent postsurgical pain (PPP) is applicable to patients who undergo total knee arthroplasty (TKA). METHODS: In this cohort study, 392 participants of a randomized study investigating the effects of anaesthesia methods and tourniquet use on TKA were divided into low-, moderate-, and high-risk groups for PPP, as suggested in the previous risk index study. Patients reported pain using the Oxford Knee Score pain subscale and Brief Pain Inventory-short form preoperatively and 3 and 12 months postoperatively. We compared the pain scores of the low- to moderate- and high-risk groups at respective time points and investigated changes in pain scores and the prevalence of PPP at 3 and 12 months after surgery. RESULTS: The high-risk group reported more pain 3 and 12 months after TKA than the low- to moderate-risk group. However, of seven variables, only a single difference reached the threshold for minimal clinical importance between the groups at 12 months. Additionally, at 12 months, the low- to moderate-risk group reported slightly worse improvements in three of seven pain variables than the high-risk group. Depending on the definition, the prevalence of PPP ranged from 2% to 29% in the low- to moderate-risk group and 4% to 41% in the high-risk group 12 months postoperatively. CONCLUSIONS: Although the investigated risk index might predict clinically important differences in PPP between the risk groups at 3 months after TKA, it seems poorly applicable for predicting PPP at 12 months after TKA. SIGNIFICANCE: Although many risk factors for persistent postsurgical pain after total knee arthroplasty have been identified, predicting the risk of this pain has remained a challenge. Results of the current study suggest that accumulation of previously presented modifiable risk factors might be associated with increased postsurgical pain at 3 months, but not at 12 months after total knee arthroplasty.

Clinical and genetic factors associated with post-operative nausea and vomiting after propofol anaesthesia.

BACKGROUND: The incidence of post-operative nausea and vomiting (PONV) remains at about 30% despite all therapeutic efforts to reduce it. The clinical risk factors guiding the prophylactic treatment are well established, but genetic factors associated with PONV remain poorly known. The aim of this study was to explore clinical and genetic factors impacting PONV by performing a genome-wide association study (GWAS) together with relevant clinical factors as covariates, and systematically attempt to replicate previously reported PONV associations. Relevant clinical factors are explored with logistic regression model. METHODS: This was an observational case control study in Helsinki University Hospital between 1 August 2006 and 31 December 2010. One thousand consenting women with elevated risk for PONV, undergoing breast cancer surgery with standardised propofol anaesthesia and antiemetics. After exclusions for clinical reasons and failed genotyping, 815 patients were included with 187 PONV cases and 628 controls. Emergence of PONV up to 7th post-operative day was recorded. PONV at 2-24 h after surgery was selected to be the primary outcome. The GWAS explored associations between PONV and 653 034 genetic variants. Replication attempts included 31 variants in 16 genes. RESULTS: The overall incidence of PONV up to 7th post-operative day was 35%, where 3% had PONV at 0-2 h and 23% at 2-24 h after surgery. Age, American Society of Anaesthesiologists status, the amount of oxycodone used in the post-anaesthesia care unit, smoking status, previous PONV, and history of motion sickness were statistically significant predictive factors in the logistic model. The receiver operating characteristic-area under the curve of 0.75 (95% CI 0.71-0.79) was calculated for the model. The GWAS identified six variants with suggestive association to PONV (p < 1 × 10-5 ). Of the previously reported variants, association with the DRD2 variant rs18004972 (TaqIA) was replicated (p = .028). CONCLUSIONS: Our GWAS approach did not identify any high-impact PONV susceptibility variants. The results provide some support for a role of dopamine D2 receptors in PONV.

Fat tissue is a poor predictor of 1 year outcomes after total knee arthroplasty: A secondary analysis of a randomized clinical trial.

BACKGROUND AND OBJECTIVE: Obesity may increase the risk of adverse events after total knee arthroplasty (TKA). Although body mass index (BMI) is commonly used in categorizing obesity, its accuracy is limited. Body fat percentage (BFP) might indicate adiposity status and predict arthroplasty-related outcomes better than BMI. We investigated whether BFP is predictive of TKA-related outcomes. METHODS: In this secondary analysis, BFP was measured preoperatively from 294 participants of a randomized trial that investigated the effects of tourniquet and anesthesia methods on TKA. Data concerning in-hospital assessments and events were collected. Knee range of motion (ROM) was measured, the Brief Pain Inventory-short form and Oxford Knee Score questionnaires were used to collect data on patient-reported pain and function, and the 15-dimensional health-related questionnaire was used to assess quality of life preoperatively and 3 and 12 months postoperatively. The patients reported satisfaction to TKA 3 and 12 months postoperatively. Data concerning infectious and thromboembolic events within 90 postoperative days and revision surgery, manipulation under anesthesia, and mortality within 1 year were collected. A separate post hoc analysis was performed for 399 participants to assess the effects of BMI on the respective outcomes. RESULTS: A 1-unit increase in BFP affected the ROM by -0.37° (95% confidence interval (CI) = -0.60 to -0.13) 12 months after surgery. BFP was not significantly associated with the operation time or adverse events. However, the number of most adverse events remained too low for adjusted analysis. A 1-unit increase in BMI increased the operation time by 0.57 min (95% CI = 0.10 to 1.04) and affected the ROM by -0.47° (95% CI = -0.74 to -0.20) 12 months postoperatively. Neither BFP nor BMI was significantly associated with acute pain, pain management, length of stay, or with pain, function, quality of life, or satisfaction to TKA at 12 months after surgery. CONCLUSIONS: BFP seems to be a poor predictor of in-hospital results and of patient-reported outcomes 1 year after TKA. TWITTER HANDLE: In this secondary analysis of a randomized trial, body fat percentage was poorly predictive of clinical outcomes during hospital stay and of patient-reported outcomes 1 year after TKA.

Regional anaesthesia in patients on antithrombotic drugs - a joint ESAIC/ESRA guideline: Endorsement by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the clinical practice guideline Regional anaesthesia in patients on antithrombotic drugs - a joint ESAIC/ESRA guideline. This clinical practice guideline serves as a useful decision aid for Nordic anaesthesiologists providing regional anaesthesia to adult patients on antithrombotic drugs.

Therapeutics and COVID-19-A living WHO guideline: Endorsement by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the Living WHO guideline on therapeutics and COVID-19. This trustworthy continuously updated guideline serves as a highly useful decision aid for Nordic anaesthesiologists caring for patients with COVID-19.

Transfusion strategies in bleeding critically ill adults: A clinical practice guideline from the European Society of Intensive Care Medicine: Endorsement by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the clinical practice guideline Transfusion strategies in bleeding critically ill adults: a clinical practice guideline from the European Society of Intensive Care Medicine. This trustworthy clinical practice guideline serves as a useful decision aid for Nordic anaesthesiologists caring for critically ill patients with bleeding.

Surviving sepsis campaign: International guidelines for management of sepsis and septic shock in adults 2021 - endorsement by the Scandinavian society of anaesthesiology and intensive care medicine.

The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the clinical practice guideline Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. The guideline serves as a useful bedside decision aid for clinicians managing adults with suspected and confirmed septic shock and sepsis-associated organ dysfunction.

Clinical practice guideline on the management of septic shock and sepsis-associated organ dysfunction in children: Endorsement by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

BACKGROUND: The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the clinical practice guideline Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children. The guideline can serve as a useful decision aid for clinicians managing children with suspected and confirmed septic shock and sepsis-associated organ dysfunction.

Anesthesia Method, Tourniquet Use, and Persistent Postsurgical Pain after Total Knee Arthroplasty: A Prespecified Secondary Analysis of a Randomized Trial.

BACKGROUND: Persistent postsurgical pain after total knee arthroplasty is a common problem and a major reason for patient dissatisfaction. This secondary analysis aimed to investigate the effects of anesthesia (spinal vs. general) and tourniquet use on persistent pain after total knee arthroplasty. METHODS: In this secondary analysis of a previously presented parallel, single-center, randomized trial, 404 patients scheduled for total knee arthroplasty were randomized to spinal versus general anesthesia and no-tourniquet versus tourniquet groups. Patients assessed pain using the Brief Pain Inventory-short form preoperatively and 3 and 12 months postoperatively. The prespecified main outcome was the change in "average pain" measured with numerical 0 to 10 rating scale 1 yr postoperatively. The threshold for clinical importance between groups was set to 1.0. RESULTS: The change in average pain scores 1 yr postoperatively did not differ between the spinal and general anesthesia groups (-2.6 [SD 2.5] vs. -2.3 [SD 2.5], respectively; mean difference, -0.4; 95% CI, -0.9 to 0.1; P = 0.150). The no-tourniquet group reported a smaller decrease in the average pain scores than the tourniquet group (-2.1 [SD 2.7] vs. -2.8 [SD 2.3]; mean difference, 0.6; 95% CI, 0.1 to 1.1; P = 0.012). After 1 yr, the scores concerning the mean of four pain severity variables (numerical rating scale) decreased more in the spinal than in the general anesthesia group (-2.3 [SD 2.2] vs. -1.8 [SD 2.1]; mean difference, -0.5; 95% CI, -0.9 to -0.05; P = 0.029) and less in the no-tourniquet than in the tourniquet group (-1.7 [SD 2.3] vs. -2.3 [SD 2.0]; mean difference, 0.6; 95% CI, 0.2 to 1.0; P = 0.005). None of the differences in pain scores reached the threshold for clinical importance. CONCLUSIONS: The type of anesthesia (spinal vs. general) or tourniquet use has no clinically important effect on persistent postsurgical pain after total knee arthroplasty.

Use of a Tourniquet and Spinal Anesthesia Increases Satisfactory Outcomes After Total Knee Arthroplasty: A Randomized Study.

BACKGROUND: Total knee arthroplasty (TKA) is usually performed successfully with or without a tourniquet and under spinal anesthesia (SA) or general anesthesia (GA). However, 10% to 34% of patients experience dissatisfaction and pain after TKA. We aimed to compare the effects of tourniquet use and SA or GA on TKA outcomes. METHODS: We randomly assigned 404 patients to 4 study groups: SA without a tourniquet (NT/SA), SA with a tourniquet (T/SA), GA without a tourniquet (NT/GA), and GA with a tourniquet (T/GA). The primary outcome was the change in the Oxford Knee Score (OKS) at 1 year postoperatively. Secondary outcomes included a satisfactory TKA outcome assessed using the OKS minimal important change (MIC) and OKS patient acceptable symptom state (PASS), adverse events, and quality of life using the 15-dimensional health-related quality of life tool. RESULTS: At 1 year, the OKS was obtained for 381 patients. In the 2-group comparisons, the tourniquet did not affect the OKS improvement. The SA group had more substantial improvement in the OKS than the GA group (16.21 compared with 14.08 a mean difference of 2.13; 95% confidence interval [CI], 0.55 to 3.71; p = 0.008). In the 4-group comparisons, the T/SA group had more substantial improvements in the OKS than the NT/GA group (16.87 compared with 13.65, a mean difference of 3.2; 95% CI, 0.28 to 6.17; p = 0.026). The SA group reached the OKS MIC more frequently than the GA group (91.7% compared with 81.7%; odds ratio [OR] = 2.49 [95% CI, 1.32 to 4.69]; p = 0.005). The SA group also reached the OKS PASS more frequently than the GA group (86.0% compared with 75.7%; OR = 2.00 [95% CI, 1.18 to 3.39]; p = 0.010). The T/SA group had significantly more patients reaching the OKS MIC than the NT/GA group (95.7% compared with 79.6%; p = 0.005) and more patients reaching the OKS PASS than the NT/GA group (92.6% compared with 74.5%; p = 0.004). No differences were seen with respect to adverse events in any comparisons. CONCLUSIONS: The tourniquet had no detrimental effects on the outcomes of TKA. SA had a positive effect on the OKS. The use of SA combined with a tourniquet resulted in the best improvement in OKS and the highest proportion of satisfactory outcomes with TKA. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.