An Immersive Virtual Reality Intervention for Preoperative Anxiety and Distress Among Adults Undergoing Oncological Surgery: Protocol for a 3-Phase Development and Feasibility Trial.

BACKGROUND: Preoperative state anxiety (PSA) is distress and anxiety directly associated with perioperative events. PSA is associated with negative postoperative outcomes such as longer hospital length of stay, increased pain and opioid use, and higher rates of rehospitalization. Psychological prehabilitation, such as education, exposure to hospital environments, and relaxation strategies, has been shown to mitigate PSA; however, there are limited skilled personnel to deliver such interventions in clinical practice. Immersive virtual reality (VR) has the potential for greater accessibility and enhanced integration into an immersive and interactive experience. VR is rarely used in the preoperative setting, but similar forms of stress inoculation training involving exposure to stressful events have improved psychological preparation in contexts such as military deployment. OBJECTIVE: This study seeks to develop and investigate a targeted PSA intervention in patients undergoing oncological surgery using a single preoperative VR exposure. The primary objectives are to (1) develop a novel VR program for patients undergoing oncological surgery with general anesthesia; (2) assess the feasibility, including acceptability, of a single exposure to this intervention; (3) assess the feasibility, including acceptability, of outcome measures of PSA; and (4) use these results to refine the VR content and outcome measures for a larger trial. A secondary objective is to preliminarily assess the clinical utility of the intervention for PSA. METHODS: This study comprises 3 phases. Phase 1 (completed) involved the development of a VR prototype targeting PSA, using multidisciplinary iterative input. Phase 2 (data collection completed) involves examining the feasibility aspects of the VR intervention. This randomized feasibility trial involves assessing the novel VR preoperative intervention compared to a VR control (ie, nature trek) condition and a treatment-as-usual group among patients undergoing breast cancer surgery. Phase 3 will involve refining the prototype based on feasibility findings and input from people with lived experience for a future clinical trial, using focus groups with participants from phase 2. RESULTS: This study was funded in March 2019. Phase 1 was completed in April 2020. Phase 2 data collection was completed in January 2024 and data analysis is ongoing. Focus groups were completed in February 2024. Both the feasibility study and focus groups will contribute to further refinement of the initial VR prototype (phase 3), with the final simulation to be completed by mid-2024. CONCLUSIONS: The findings from this work will contribute to the limited body of research examining feasible and broadly accessible interventions for PSA. Knowledge gained from this research will contribute to the final development of a novel VR intervention to be tested in a large population of patients with cancer before surgery in a randomized clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT04544618; https://www.clinicaltrials.gov/study/NCT04544618. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55692.

The effect of intravenous tranexamic acid on visual clarity in arthroscopic shoulder surgery compared to epinephrine and a placebo: a double-blinded, randomized controlled trial.

BACKGROUND: The addition of epinephrine in irrigation fluid and the intravenous or local administration of tranexamic acid have independently been reported to decrease bleeding, thereby improving surgeons' visualization during arthroscopic shoulder procedures. No study has compared the effect of intravenous tranexamic acid, epinephrine in the irrigation fluid, or the combination of both tranexamic acid and epinephrine on visual clarity during shoulder arthroscopy with a placebo group. We hypothesized that intravenous tranexamic acid is more effective than epinephrine mixed in the irrigation fluid in improving visualization during shoulder arthroscopy, with no additive effect when both are used. METHODS: Patients aged ≥18 years undergoing shoulder arthroscopy were randomized into one of 4 study arms: (1) saline irrigation fluid (placebo); (2) epinephrine (0.33 mL of 1:1000 per liter) mixed in irrigation fluid (EPI); (3) 1 g intravenous tranexamic acid (TXA); and (4) epinephrine and tranexamic acid combined (TXA + EPI). Visualization was rated intraoperatively on a scale from 0, indicating poor clarity, to 3, indicating excellent clarity, every 15 minutes and overall. The primary outcome measure was the overall rating of visualization. A stepwise linear regression was performed using visualization as the dependent variable and independent variables including presence or absence of epinephrine and tranexamic acid, surgery duration, complexity, mean arterial pressure, increase in pump pressure, and volume of irrigation fluid. RESULTS: One hundred twenty-eight patients (mean age 56 years) were randomized. Mean visual clarity for the placebo, TXA, EPI, and TXA + EPI groups were 2.0 (±0.6), 2.0 (±0.6), 2.6 (±0.5), and 2.7 (±0.5), respectively (P < .001). The presence or absence of epinephrine was the most significant predictor of visual clarity (P < .001). Tranexamic acid presence or absence had no effect. No adverse events were recorded in any of the groups. CONCLUSION: Intravenous tranexamic acid is not an effective alternative to epinephrine in irrigation fluid to improve visualization during routine arthroscopic shoulder surgeries, and there is no additive effect when both are used.

Analgesic duration of interscalene block after outpatient arthroscopic shoulder surgery with intravenous dexamethasone, intravenous dexmedetomidine, or their combination: a randomized-controlled trial.

PURPOSE: Both intravenous dexamethasone and dexmedetomidine prolong the analgesic duration of interscalene blocks (ISB) after arthroscopic shoulder surgery. This study compared their relative effectiveness and the benefit of their use in combination. METHODS: This single-centre, double-blinded, parallel three-group superiority trial randomized 198 adult patients undergoing ambulatory arthroscopic shoulder surgery. Patients received preoperative ISB with 30 mL 0.5% bupivacaine and 50 µg dexmedetomidine or 4 mg dexamethasone or both of these agents as intravenous adjuncts. The primary outcome was analgesic block duration. Secondary outcomes included the quality of recovery 15 score (range: 0-150) on day 1 and postoperative neurologic symptoms in the surgical arm. RESULTS: Block durations (n = 195) with dexamethasone (median [range], 24.5 [2.0-339.5] hr) and both adjuncts (24.0 [1.5-157.0] hr) were prolonged compared with dexmedetomidine (16.0 [1.5-154.0] hr). When analyzed by linear regression after an unplanned log transformation because of right-skewed data, the corresponding prolongations of block duration were 59% (95% confidence interval [CI], 28 to 97) and 46% (95% CI, 18 to 80), respectively (both P < 0.001). The combined adjuncts were not superior to dexamethasone alone (-8%; 95% CI, -26 to 14; P = 0.42). Median [IQR] quality of recovery 15 scores (n = 197) were significantly different only between dexamethasone (126 [79-149]) and dexmedetomidine (118.5 [41-150], P = 0.004), but by an amount less than the 8-point minimum clinically important difference. CONCLUSION: Dexamethasone is superior to dexmedetomidine as an intravenous adjunct for prolongation of bupivacaine-based ISB analgesic duration. There was no additional benefit to using both adjuncts in combination. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT03270033); registered 1 September 2017.

RéSUMé: OBJECTIF: La dexaméthasone et la dexmédétomidine intraveineuses prolongent toutes deux la durée analgésique des blocs interscaléniques (BIS) après une chirurgie arthroscopique de l'épaule. Cette étude a comparé leur efficacité relative et les avantages d'une utilisation des deux agents en combinaison. MéTHODE: Cette étude de supériorité monocentrique en trois groupes parallèles à double insu a randomisé 198 patients adultes subissant une chirurgie arthroscopique de l'épaule en ambulatoire. Les patients ont reçu un BIS préopératoire composé de 30 mL de bupivacaïne 0,5 % avec 50 µg de dexmédétomidine, 4 mg de dexaméthasone, ou la combinaison de ces deux agents comme adjuvants intraveineux. Le critère d'évaluation principal était la durée analgésique du bloc. Les critères d'évaluation secondaires comprenaient le score de qualité de récupération (QoR) 15 (plage : 0-150) au jour 1 et les symptômes neurologiques postopératoires dans le bras opéré. RéSULTATS: Les durées des blocs (n = 195) avec la dexaméthasone (médiane [plage], 24,5 [2,0-339,5] heures) et la combinaison des deux adjuvants (24,0 [1,5-157,0] heures) ont été prolongées par rapport à la dexmédétomidine (16,0 [1,5-154,0] heures). Lorsqu'elles ont été analysées par régression linéaire après une transformation logarithmique non planifiée en raison de données biaisées vers la droite, les prolongations correspondantes de la durée du bloc étaient de 59 % (intervalle de confiance [IC] 95 %, 28 à 97) et de 46 % (IC 95 %, 18 à 80), respectivement (les deux P < 0,001). La combinaison des adjuvants n'était pas supérieure à la dexaméthasone seule (-8 %; IC 95 %, -26 à 14; P = 0,42). Les scores médians [ÉIQ] de qualité de récupération 15 (n = 197) n'étaient significativement différents qu'entre la dexaméthasone (126 [79-149]) et la dexmédétomidine (118,5 [41-150], P = 0,004), mais la différence observée était inférieure à la différence minimale de 8 points nécessaire pour être considérée cliniquement importante. CONCLUSION: La dexaméthasone est supérieure à la dexmédétomidine en tant qu'adjuvant intraveineux pour prolonger la durée analgésique d'un BIS à base de bupivacaïne. Aucun avantage supplémentaire n'a été observé lors de l'utilisation combinée des deux adjuvants. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT03270033); enregistrée le 1er septembre 2017.

Does eliminating the preoperative history and physical make a difference in low-risk cataract surgery patients? A before and after study of 30-day morbidity and mortality.

OBJECTIVE: To evaluate the safety of omitting the conventional preoperative history and physical examination (H&P) for low-risk cataract surgery patients. DESIGN: Comparison of outcomes before and after the January 1, 2015 system wide implementation of a program that eliminated the conventional preoperative H&P for low-risk patients as identified by a 12-item risk stratification questionnaire. PARTICIPANTS: Two separate groups of Winnipeg residents who had cataract surgery at the city's sole ophthalmological referral centre between July 1 and December 31, 2014 (preimplementation reference group) or between October 1, 2015 and March 31, 2016 (postimplementation intervention group). METHODS: A detailed chart review was completed for cataract surgery patients who experienced a postoperative medical event (a composite of death or hospital admission or emergency department visit, identified within administrative databases) within 30 days of surgery. Nonfatal events were captured for all 7 hospitals and urgent care centres in the city, including the ophthalmological referral centre. RESULTS: Postoperative medical events occurred in 114 of 2981 (3.82%) intervention group surgeries and 125 of 3037 (4.12%) reference group surgeries (Relative risk 0.92, 95% confidence interval 0.72 to 1.19, p = 0.6 Fisher exact test). Subgroup analyses of major medical events and medical events by affected organ system yielded no significant differences between the 2 groups. In the opinion of the physician chart reviewers, none of the events among low-risk patients in the intervention group were related to the omission of a conventional preoperative H&P. CONCLUSIONS: The risk of adverse medical events within 30 days of cataract surgery was not higher after the omission of the conventional preoperative H&P in patients screened to be low risk by a validated preoperative questionnaire.

Effect of dexamethasone dose and route on the duration of interscalene brachial plexus block for outpatient arthroscopic shoulder surgery: a randomized controlled trial.

PURPOSE: Dexamethasone prolongs the duration of interscalene block, but the benefits of higher doses and perineural vs intravenous administration remain unclear. METHODS: This factorial design, double-blinded trial randomized 280 adult patients undergoing ambulatory arthroscopic shoulder surgery at a single centre in a 1:1:1:1 ratio. Patients received ultrasound-guided interscalene block with 30 mL 0.5% bupivacaine and 4 mg or 8 mg dexamethasone by either the perineural or intravenous route. The primary outcome (block duration measured as the time of first pain at the surgical site) and secondary outcomes (adverse effects, postoperative neurologic symptoms) were assessed by telephone. In this superiority trial, the predetermined minimum clinically important difference for comparisons between doses and routes was 3.0 hr. RESULTS: The perineural route significantly prolonged the mean block duration by 2.0 hr (95% confidence interval [CI], 0.4 to 3.5 hr; P = 0.01), but 8 mg of dexamethasone did not significantly prolong the mean block duration compared with 4 mg (1.3 hr; 95% CI, -0.3 to 2.9 hr, P = 0.10), and there was no significant statistical interaction (P = 0.51). The mean (95% CI) block durations, in hours, were 24.0 (22.9 to 25.1), 24.8 (23.2 to 26.3), 25.4 (23.8 to 27.0), and 27.2 (25.2 to 29.3) for intravenous doses of 4 and 8 mg and perineural doses of 4 and 8 mg, respectively. There were no marked differences in side effects between groups. At 14 postoperative days, 57 (20.4%) patients reported neurologic symptoms, including dyspnea and hoarseness. At six months postoperatively, only six (2.1%) patients had residual symptoms, with four (1.4%) patients' symptoms unlikely related to interscalene block. CONCLUSION: Compared with the intravenous route, perineural dexamethasone prolongs the mean interscalene block duration by a small amount that may or may not be clinically significant, regardless of dose. However, the difference in mean block durations between 8 mg and 4 mg of dexamethasone is highly unlikely to be clinically important, regardless of the administration route. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02426736). Registered 14 April 2015.

A matched cohort study of postoperative outcomes in obstructive sleep apnea: could preoperative diagnosis and treatment prevent complications?

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased risk of postoperative complications. The authors investigated whether preoperative diagnosis and prescription of continuous positive airway pressure therapy reduces these risks. METHODS: Matched cohort analysis of polysomnography data and Manitoban health administrative data (1987 to 2008). Postoperative outcomes in adult OSA patients up to 5 yr before (undiagnosed OSA, n = 1,571), and any time after (diagnosed OSA, n = 2,640) polysomnography and prescription of continuous positive airway pressure therapy for a new diagnosis of OSA, were compared with controls at low risk of having sleep apnea (n = 16,277). Controls were matched by exact procedure, indication, and approximate date of surgery. Procedures used to treat sleep apnea were excluded. Follow-up was at least 7 postoperative days. Results were reported as odds ratio (95% CI) for OSA or subgroup versus controls. RESULTS: In multivariate analyses, the risk of respiratory complications (2.08 [1.35 to 3.19], P < 0.001) was similarly increased for both undiagnosed and diagnosed OSA. The risk of cardiovascular complications, primarily cardiac arrest and shock, was significantly different (P = 0.009) between undiagnosed OSA (2.20 [1.16 to 4.17], P = 0.02) and diagnosed OSA patients (0.75 [0.43 to 1.28], P = 0.29). For both outcomes, OSA severity, type of surgery, age, and other comorbidities were also important risk modifiers. CONCLUSIONS: Diagnosis of OSA and prescription of continuous positive airway pressure therapy were associated with a reduction in postoperative cardiovascular complications. Despite limitations in the data, these results could be used to justify and inform large efficacy trials of perioperative continuous positive airway pressure therapy in OSA patients.

Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidney function.

BACKGROUND: Hydroxyethyl starches (HES) are synthetic colloids commonly used for fluid resuscitation to replace intravascular volume, yet they have been increasingly associated with adverse effects on kidney function. This is an update of a Cochrane review first published in 2010. OBJECTIVES: To examine the effects of HES on kidney function compared to other fluid resuscitation therapies in different patient populations. SEARCH METHODS: We searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library), MEDLINE, EMBASE, MetaRegister and reference lists of articles. The most recent search was completed on November 19, 2012. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs in which HES was compared to an alternate fluid therapy for the prevention or treatment of effective intravascular volume depletion. Primary outcomes were renal replacement therapy (RRT), author-defined kidney failure and acute kidney injury (AKI) as defined by the RIFLE criteria. DATA COLLECTION AND ANALYSIS: Screening, selection, data extraction and quality assessments for each retrieved article were carried out by two authors using standardised forms. All outcomes were analysed using relative risk (RR) and 95% confidence intervals (95% CI). Authors were contacted when published data were incomplete. Preplanned sensitivity and subgroup analyses were performed after data were analysed with a random-effects model. MAIN RESULTS: This review included 42 studies (11,399 patients) including 19 studies from the original review (2010), as well as 23 new studies. Fifteen studies were excluded from the original review (nine retracted from publication due to concerns about integrity of data and six lacking individual patient creatinine data for the calculation of RIFLE criteria). Overall, there was a significant increase in the need for RRT in the HES treated individuals compared to individuals treated with other fluid therapies (RR 1.31, 95% CI 1.16 to 1.49; 19 studies, 9857 patients) and the number with author-defined kidney failure (RR 1.59, 95% CI 1.26 to 2.00; 15 studies, 1361 patients). The RR of AKI based on RIFLE-F (failure) criteria also showed an increased risk of AKI in individuals treated with HES products (RR 1.14, 95% CI 1.01 to 1.30; 15 studies, 8402 participants). The risk of meeting urine output and creatinine based RIFLE-R (risk) criteria for AKI was in contrast in favour of HES therapies (RR 0.95, 95% CI 0.91 to 0.99; 20 studies, 8769 patients). However, when RIFLE-R urine output based outcomes were excluded as per study protocol, the direction of AKI risk again favoured the other fluid type, with a non-significant RR of AKI in HES treated patients (RR 1.05, 95% CI 0.97 to 1.14; 8445 patients). A more robust effect was seen for the RIFLE-I (injury) outcome, with a RR of AKI of 1.22 (95% CI 1.08 to 1.37; 8338 patients). No differences between subgroups for the RRT and RIFLE-F based outcomes were seen between sepsis versus non-sepsis patients, high molecular weight (MW) and degree of substitution (DS) versus low MW and DS (≥ 200 kDa and > 0.4 DS versus 130 kDa and 0.4 DS) HES solutions, or high versus low dose treatments (i.e. ≥ 2 L versus < 2 L). There were differences identified between sepsis versus non-sepsis subgroups for the RIFLE-R and RIFLE-I based outcomes only, which may reflect the differing renal response to fluid resuscitation in pre-renal versus sepsis-associated AKI. Overall, methodological quality of the studies was good. AUTHORS' CONCLUSIONS: The current evidence suggests that all HES products increase the risk in AKI and RRT in all patient populations and a safe volume of any HES solution has yet to be determined. In most clinical situations it is likely that these risks outweigh any benefits, and alternate volume replacement therapies should be used in place of HES products.

Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidney function.

BACKGROUND: Hydroxyethyl starches (HES) are synthetic colloids commonly used for fluid resuscitation, yet controversy exists about their impact on kidney function. OBJECTIVES: To examine the effects of HES on kidney function compared to other fluid resuscitation therapies in different patient populations. SEARCH STRATEGY: We searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library), MEDLINE, EMBASE, MetaRegister and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs in which HES was compared to an alternate fluid therapy for the prevention or treatment of effective intravascular volume depletion. Primary outcomes were renal replacement therapy (RRT), author-defined kidney failure and acute kidney injury (AKI) as defined by the RIFLE criteria. Secondary outcomes included serum creatinine and creatinine clearance. DATA COLLECTION AND ANALYSIS: Screening, selection, data extraction and quality assessments for each retrieved article were carried out by two authors using standardised forms. Authors were contacted when published data were incomplete. Preplanned sensitivity and subgroup analyses were performed after data were analysed with a random effects model. MAIN RESULTS: The review included 34 studies (2607 patients). Overall, the RR of author-defined kidney failure was 1.50 (95% CI 1.20 to 1.87; n = 1199) and 1.38 for requiring RRT (95% CI 0.89 to 2.16; n = 1236) in HES treated individuals compared with other fluid therapies. Subgroup analyses suggested increased risk in septic patients compared to non-septic (surgical/trauma) patients. Non-septic patient studies were smaller and had lower event rates, so subgroup differences may have been due to lack of statistical power in these studies. Only limited data was obtained for analysis of kidney outcomes by the RIFLE criteria. Overall, methodological quality of studies was good but subjective outcomes were potentially biased because most studies were unblinded. AUTHORS' CONCLUSIONS: Potential for increased risk of AKI should be considered when weighing the risks and benefits of HES for volume resuscitation, particularly in septic patients. Large studies with adequate follow-up are required to evaluate the renal safety of HES products in non-septic patient populations. RIFLE criteria should be applied to evaluate kidney function in future studies of HES and, where data is available, to re-analyse those studies already published. There is inadequate clinical data to address the claim that safety differences exist between different HES products.

Expression of monolysocardiolipin acyltransferase activity is regulated in concert with the level of cardiolipin and cardiolipin biosynthesis in the mammalian heart.

BACKGROUND: Monolysocardiolipin acyltransferase (MLCL AT) catalyzes the acylation of monolysocardiolipin to cardiolipin in mammalian tissues. We previously reported that cardiac cardiolipin levels, MLCL AT and cardiolipin synthase activities were all elevated in rats made hyperthyroid by thyroxine treatment. In this study, we examined if cardiac mitochondrial MLCL AT activity was dependent upon the biosynthesis and level of cardiolipin in the heart. Rat heart mitochondrial MLCL AT activity was determined under conditions in which the levels of cardiac cardiolipin and cardiolipin synthase activity were either reduced or unaltered using four different disease models in the rat. In addition, these parameters were examined in a murine model of cardiac cell differentiation. RESULTS: In rats made hypothyroid by treatment with 6-n-propyl-2-thiouracil in the drinking water for 34 days, cardiac cardiolipin content was decreased 29% (p < 0.025) and this was associated with a 32% decrease (p < 0.025) in cardiolipin synthase and a 35% reduction (p < 0.025) in MLCL AT activities. Streptozotocin-induced diabetes or hyperinsulinemia in rats did not affect cardiac cardiolipin content nor MLCL AT and cardiolipin synthase activities. Finally, cardiolipin content, MLCL AT and cardiolipin synthase activities were unaltered during murine P19 teratocarcinoma cell differentiation into cardiac myocytes. In all models, phospholipase A2 activities were unaltered compared with controls. CONCLUSION: We propose a general model in which the expression of MLCL AT activity is regulated in concert with the biosynthesis and level of cardiolipin in the heart.