Evaluation of a Hyperbaric Oxygen Therapy Intervention in Individuals with Fibromyalgia.

OBJECTIVE: To evaluate the feasibility and safety of hyperbaric oxygen therapy (HBOT) in patients with fibromyalgia (FM). DESIGN: A cohort study with a delayed treatment arm used as a comparator. SETTING: Hyperbaric Medicine Unit, Toronto General Hospital, Ontario, Canada. SUBJECTS: Eighteen patients diagnosed with FM according to the American College of Rheumatology and a score ≥60 on the Revised Fibromyalgia Impact Questionnaire. METHODS: Participants were randomized to receive immediate HBOT intervention (n = 9) or HBOT after a 12-week waiting period (n = 9). HBOT was delivered at 100% oxygen at 2.0 atmospheres per session, 5 days per week, for 8 weeks. Safety was evaluated by the frequency and severity of adverse effects reported by patients. Feasibility was assessed by recruitment, retention, and HBOT compliance rates. Both groups were assessed at baseline, after HBOT intervention, and at 3 months' follow-up. Validated assessment tools were used to evaluate pain, psychological variables, fatigue, and sleep quality. RESULTS: A total of 17 patients completed the study. One patient withdrew after randomization. HBOT-related adverse events included mild middle-ear barotrauma in three patients and new-onset myopia in four patients. The efficacy of HBOT was evident in most of the outcomes in both groups. This improvement was sustained at 3-month follow-up assessment. CONCLUSION: HBOT appears to be feasible and safe for individuals with FM. It is also associated with improved global functioning, reduced symptoms of anxiety and depression, and improved quality of sleep that was sustained at 3-month follow-up assessment.

Hyperbaric oxygen and focused rehabilitation program: a feasibility study in improving upper limb motor function after stroke.

Neuroplasticity and recovery after stroke can be enhanced by a rehabilitation program pertinent to upper limb motor function exercise and mental imagery (EMI) as well as hyperbaric oxygen therapy (HBOT). We assessed feasibility and safety of the combined approach utilizing both HBOT and EMI, and to derive preliminary estimates of its efficacy. In this randomized controlled trial, 27 patients with upper extremity hemiparesis at 3-48 months after stroke were randomized to receive either a complementary rehabilitation program of HBOT-EMI (intervention group), or EMI alone (control group). Feasibility and safety were assessed as total session attendance, duration of sessions, attrition rates, missing data, and intervention-related adverse events. Secondary clinical outcomes were assessed with both objective tools and self-reported measures at baseline, 8 weeks (end of treatment), and 12-weeks follow-up. Session attendance, duration, and attrition rate did not differ between the groups; there were no serious adverse events. Compared with baseline, there were significant sustained improvements of objective and subjective outcomes' measures in the intervention group, and a single improvement in an objective measure in the control group. Between-group outcome comparisons were not statistically significant. This study demonstrated that the combination HBOT-EMI was a safe and feasible approach in patients recovering from chronic stroke. There were also trends for improved motor function of the affected upper limb after the treatments. ClinicalTrials.gov registration no.: NCT02666469. Novelty HBOT combined with an upper limb exercise and mental imagery rehabilitation program is feasible and safe in chronic stroke patients. This combined approach showed trends for improved functional recovery.

Cerebral oximetry and postoperative delirium after cardiac surgery: a randomised, controlled trial.

Postoperative delirium is associated with increased morbidity and mortality. We hypothesised that restoration of regional cerebral oxygen desaturation would reduce the incidence of postoperative delirium in elderly patients after cardiac surgery. After institutional ethics review board approval and informed consent, a double-blinded, prospective, randomised, controlled trial was conducted in patients ≥ 60 years of age undergoing cardiac surgery with cardiopulmonary bypass. In the intervention group, an algorithm was commenced if regional cerebral oxygen saturation decreased below 75% of baseline value for 1 min or longer. In the control group, the cerebral oximetry monitor screen was electronically blinded. Assessment of delirium was performed with confusion assessment method for intensive care unit or confusion assessment method after discharge from intensive care unit at 12-h intervals for seven postoperative days. Postoperative delirium was present in 30 out of 123 (24.4%) and 31 out of 126 (24.6%) patients in the intervention and control groups, respectively, odds ratio 0.98 (95%CI 0.55-1.76), p = 0.97. Postoperative delirium was present in 20 (71%) out of 28 and in 41 (18%) out of 221 patients with baseline regional cerebral oxygen saturation ≤ 50, or > 50%, respectively, p = 0.0001. Higher baseline regional cerebral oxygen saturation and body mass index were protective against postoperative delirium. Restoration of regional cerebral oxygen desaturation did not result in lower postoperative delirium after cardiac surgery. Pre-operative regional cerebral oxygen saturation ≤ 50% was associated with increased postoperative delirium rates in elderly patients following cardiac surgery.

Delirium after transcatheter aortic valve implantation via the femoral or apical route.

We thought that delirium might be less frequent after transcatheter aortic valve implantation via the femoral artery compared with via the cardiac apex. We reviewed 210 patients who underwent transcatheter aortic valve implantation between January 2009 and October 2014. The proportion (95% CI) of patients who suffered delirium in the 3 days after valve implantation were: 10 (3-16%) in 105 patients who had transfemoral implantation; and 35 (25-45%) in 105 patients who had transapical implantation, p = 0.0001. The variables that independently associated with postoperative delirium were age, male sex and the transapical approach. The median (IQR [range]) hospital stay was 7 (5-13 [2-41]) days and 10 (7-15 [2-64]) days, respectively, p = 0.004. Future trials should focus on different peri-operative management strategies to reduce delirium rates after transcatheter aortic valve implantation, particularly in older men having implantations via the cardiac apex.

Diastolic dysfunction, cardiopulmonary bypass, and atrial fibrillation after coronary artery bypass graft surgery.

BACKGROUND: Atrial fibrillation (AF) is a common complication after coronary artery bypass graft (CABG) surgery, and is associated with increased morbidity, mortality, and utilization of healthcare resources. Diastolic dysfunction (DD) causes a range of changes in left atrial structure and function that may predispose patients to increased risk of AF. We hypothesized that patients with either new or worsened grade of DD after cardiopulmonary bypass (CPB) would have higher prevalence of AF after CABG surgery. The current study sought to determine an association between the dynamic changes in diastolic function during the perioperative period and postoperative AF in patients undergoing CABG surgery. METHODS: A total of 109 patients undergoing elective CABG surgery were assessed for the presence of DD before and after CPB. All patients were monitored for the development of AF after surgery for the entire hospital stay. RESULTS: DD was present in 89 (81%) and 91 (83%) patients before and after CPB. Thirty-four (31%) patients had either new or worsened grade of DD after CPB. Postoperative AF was present in 30 (27.5%) patients, including 15 (44%) patients with either new or worsened DD, and 15 (20%) patients with either unchanged or improved DD (P=0.009). Independent predictors of postoperative AF included age ≥65 yr [odds ratio (OR) 4.207, 95% confidence interval (CI) 1.527, 11.588], and new or worsened DD (OR 4.145, 95% CI 1.519, 11.356). CONCLUSIONS: New or worsened DD after CABG surgery is associated with an increased incidence of postoperative AF. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov; unique identifier NCT00188903.

The association between tranexamic acid and convulsive seizures after cardiac surgery: a multivariate analysis in 11 529 patients.

Because of a lack of contemporary data regarding seizures after cardiac surgery, we undertook a retrospective analysis of prospectively collected data from 11 529 patients in whom cardiopulmonary bypass was used from January 2004 to December 2010. A convulsive seizure was defined as a transient episode of disturbed brain function characterised by abnormal involuntary motor movements. Multivariate regression analysis was performed to identify independent predictors of postoperative seizures. A total of 100 (0.9%) patients developed postoperative convulsive seizures. Generalised and focal seizures were identified in 68 and 32 patients, respectively. The median (IQR [range]) time after surgery when the seizure occurred was 7 (6-12 [1-216]) h and 8 (6-11 [4-18]) h, respectively. Epileptiform findings on electroencephalography were seen in 19 patients. Independent predictors of postoperative seizures included age, female sex, redo cardiac surgery, calcification of ascending aorta, congestive heart failure, deep hypothermic circulatory arrest, duration of aortic cross-clamp and tranexamic acid. When tested in a multivariate regression analysis, tranexamic acid was a strong independent predictor of seizures (OR 14.3, 95% CI 5.5-36.7; p < 0.001). Patients with convulsive seizures had 2.5 times higher in-hospital mortality rates and twice the length of hospital stay compared with patients without convulsive seizures. Mean (IQR [range]) length of stay in the intensive care unit was 115 (49-228 [32-481]) h in patients with convulsive seizures compared with 26 (22-69 [14-1080]) h in patients without seizures (p < 0.001). Convulsive seizures are a serious postoperative complication after cardiac surgery. As tranexamic acid is the only modifiable factor, its administration, particularly in doses exceeding 80 mg.kg(-1), should be weighed against the risk of postoperative seizures.

Post-operative hypercapnia-induced hyperpnoea accelerates recovery from sevoflurane anaesthesia: a prospective randomised controlled trial.

BACKGROUND: The time to recovery from vapour anaesthesia is shortened by an increase in ventilation while maintaining normocapnia. Hypercapnia during emergence from anaesthesia in spontaneously breathing patients also increases anaesthetic clearance from the brain by increasing cerebral blood flow. We hypothesised that hypercapnia-induced hyperpnoea accelerates emergence from sevoflurane anaesthesia compared to the standard anaesthesia protocol. METHODS: After Ethics Review Board approval, 44 ASA I-III patients undergoing elective gynaecological surgery were randomised after surgery to either hypercapnic hyperpnoea or control groups. In the hypercapnic hyperpnoea group, the end-tidal CO2 was adjusted to a range of 6.0-7.3 kPa to maintain a minute ventilation of 10-15 l/min. Recovery indices were compared using unpaired t-tests and ANOVA. RESULTS: Prior to extubation, minute ventilation and end-tidal CO2 in hypercapnic hyperpnoea and control groups were 10.3 ± 1.7 l/min vs. 5.4 ± 1.2 l/min (P < 0.001) and 6.6 ± 0.6 kPa and 5.2 ± 0.5 kPa (P < 0.001), respectively. Compared to control, the study group had shorter time to extubation [4.4 ± 1.3 (SD) vs. 9.8 ± 4.4 min, P < 0.01], BIS recovery to > 75 (2.4 ± 0.9 vs. 6.1 ± 3.1 min, P < 0.01), eye opening (3.9 ± 1.6 vs. 9.8 ± 6.2 min, P < 0.01), eligibility for leaving operating room (5.1 ± 1.2 vs. 11.1 ± 4.6 min, P < 0.01), and post-anaesthesia care unit (73.9 ± 14.2 vs. 89.4 ± 22.6) CONCLUSION: Hypercapnic hyperpnoea in spontaneously breathing patients halves the time of recovery from sevoflurane-induced anaesthesia in the operating room.

Genetic variation and cognitive dysfunction one year after cardiac surgery.

Various studies have implicated a potential association between candidate gene polymorphisms and postoperative cognitive dysfunction, yet corroborative studies are lacking. We investigated the variants in genes encoding platelet glycoprotein-IIIa and apolipoprotein-E and their relationship with postoperative cognitive dysfunction one year after cardiac surgery. A total of 155 patients were studied; neuropsychological testing demonstrated cognitive dysfunction in 31 (20%) patients at one-year follow-up. No differences were detected with respect to baseline characteristics, pre-operative variables and surgical data between the patients with and without cognitive dysfunction. The Pl(A2) -allele of the platelet glycoprotein-IIIa gene was present in 13 (42%) and 25 (20%) patients with and without cognitive dysfunction, respectively, p = 0.012. The apolipoprotein E-ε4 allele was present in 9 (29%) and 24 (19%) patients with and without cognitive dysfunction, respectively, p = 0.24. Both the Pl(A2) and apolipoprotein-ε4 alleles were present together in 6 (19%) and 5 (4%) patients with and without cognitive dysfunction, respectively, p = 0.003. Validation of these findings is required in age-adjusted non-surgical controls.

Measurement of forces applied during Macintosh direct laryngoscopy compared with GlideScope® videolaryngoscopy.

Laryngoscopy can induce stress responses that may be harmful in susceptible patients. We directly measured the force applied to the base of the tongue as a surrogate for the stress response. Force measurements were obtained using three FlexiForce Sensors(®) (Tekscan Inc, Boston, MA, USA) attached along the concave surface of each laryngoscope blade. Twenty-four 24 adult patients of ASA physical status 1-2 were studied. After induction of anaesthesia and neuromuscular blockade, laryngoscopy and tracheal intubation was performed using either a Macintosh or a GlideScope(®) (Verathon, Bothell, WA, USA) laryngoscope. Complete data were available for 23 patients. Compared with the Macintosh, we observed lower median (IQR [range]) peak force (9 (5-13 [3-25]) N vs 20 (14-28 [4-41]) N; p = 0.0001), average force (5 (3-7 [2-19]) N vs 11 (6-16 [1-24]) N; p = 0.0003) and impulse force (98 (42-151 [26-444]) Ns vs 150 (93-207 [17-509]) Ns; p = 0.017) with the GlideScope. Our study shows that the peak lifting force on the base of the tongue during laryngoscopy is less with the GlideScope videolaryngoscope compared with the Macintosh laryngoscope.

Increased lung clearance of isoflurane shortens emergence in obesity: a prospective randomized-controlled trial.

BACKGROUND: There is a concern that obesity may play a role in prolonging emergence from fat-soluble inhalational anaesthetics. We hypothesized that increased pulmonary clearance of isoflurane will shorten immediate recovery from anaesthesia and post-anaesthesia care unit (PACU) stay in obese patients. METHODS: After Ethics Review Board approval, 44 ASA I-III patients with BMI>30 kg/m(2) undergoing elective gynaecological or urological surgery were randomized after completion of surgery to either an isocapnic hyperpnoea (IH) or a conventional recovery (C) group. The anaesthesia protocol included propofol, fentanyl, morphine, rocuronium and isoflurane in air/O(2) . Groups were compared using unpaired t-test and ANOVA. RESULTS: Minute ventilation in the IH group before extubation was 22.6 ± 2.7 vs. 6.3 ± 1.8 l/min in the C group. Compared with C, the IH group had a shorter time to extubation (5.4 ± 2.7 vs. 15.8 ± 2.7 min, P<0.01), initiation of spontaneous ventilation (2.7 ± 2.3 vs. 6.5 ± 4.5 min, P<0.01), BIS recovery >75 (3.2 ± 2.3 vs. 8.9 ± 5.8 min, P<0.01), eye opening (4.6 ± 2.9 vs. 13.6 ± 7.1 min, P<0.01) and eligibility for leaving the operating room (7.1 ± 2.9 vs. 19.9 ± 11.9 min, P<0.01). There was no difference in time for eligibility for PACU discharge. CONCLUSION: Increasing alveolar ventilation enhances anaesthetic elimination and accelerates short-term recovery in obese patients.

Effect of sleep deprivation on labour epidural catheter placement.

BACKGROUND: Epidural catheter insertion for labour analgesia is an invasive procedure with potential serious complications, often performed by a sleep-deprived clinician. The aim of this study was to examine the effects of sleep deprivation on physicians of variable levels of experience performing this procedural skill in the clinical setting. METHODS: After institutional review board approval, anaesthetists of three levels of experience were recruited: novice residents (<30 epidurals, n=9), experienced residents (>100 epidurals, n=8), and attending anaesthetists (>500 epidurals, n=12). All participants were measured twice, rested and sleep deprived in a random order while performing a labour epidural for analgesia. Our primary outcome measures were scores achieved on the Imperial College Surgical Assessment Device (ICSAD) (measuring path length, number of movements, and time), task-specific checklist (CL), and global rating scale (GRS). Sleep deprivation was documented by the ActiGraph and Epworth sleepiness scale. RESULTS: Subjects were adequately sleep deprived for their sleep deprivation observation. Data were analysed with a two-way mixed design analysis of variance. No significant difference in the effect of sleep deprivation on performance was detected between the groups on the ICSAD measures of movement (P=0.86), path length (P=0.79), and time (P=0.80), or for the CL (P=0.65), and GRS (P=0.86). CONCLUSIONS: The performance of this procedural skill in a clinical setting does not seem to be affected by sleep deprivation irrespective of the level of experience.

A novel point-of-care information system reduces anaesthesiologists' errors while managing case scenarios.

BACKGROUND AND OBJECTIVES: The On-Line Electronic Help (OLEH) is a point-of-care information system for anaesthesia providers prepared by the European Society of Anaesthesiologists. In this preliminary study the effect of the OLEH availability on the incidence of knowledge-based errors during the management of case scenarios and participants' subjective evaluation of the OLEH were evaluated. METHODS: After a short training session, 48 anaesthesiologists (24 junior residents, 12 senior residents and 12 board-certified) were presented randomly with six computer screen-based case scenarios with, and six without, the option of using the OLEH. Two reviewers evaluated the answers independently according to preconfigured guidelines. RESULTS: The availability of the OLEH was associated with higher scores in 11 of the 12 scenarios, and with a decrease in the incidence of critical errors in 10 scenarios. Time to task completion was increased in one scenario only when the OLEH was used. The degree of professional experience was associated with better scores in five of the scenarios and with a reduced occurrence of critical errors in three scenarios. Forty-two out of 48 participants stated that finding information in the OLEH software was easy and that the system was helpful in managing the scenarios. CONCLUSIONS: This preliminary study demonstrates the potential value of the OLEH in decreasing the number of knowledge-based errors made by anaesthesiologists. According to the encouraging results, the OLEH system is currently under evaluation using full-scale simulation scenarios in an operating room environment.

Effects of denaturation and methylation on the degradation of proteins in cultured hepatoma cells and in reticulocyte cell-free systems.

Radioiodinated, native and denatured bovine serum albumin (albumin) beta-lactoglobulin and cytochrome c were introduced into hepatoma tissue culture cells by erythrocyte-ghost-mediated microinjection, and their rates of degradation were compared. Denatured albumin was degraded at 20% of the rate of undenatured albumin, denatured beta-lactoglobulin was degraded three times faster than undenatured beta-lactoglobulin, while denatured and undenatured cytochrome c were degraded at the same rate. Thus, denaturation does not affect the rates of intracellular breakdown of microinjected proteins in a simple predictable way. Exhaustive methylation did not inhibit the degradation of denatured beta-lactoglobulin or albumin, indicating that, like their undenatured counterparts, they are not degraded via the ubiquitin pathway. In reticulocyte lysates, in the presence of ATP, denatured albumin and beta-lactoglobulin were broken down at slightly slower rates than the parent proteins. Exhaustive methylation of both denatured and undenatured proteins completely abolished their ATP-dependent breakdown. This inhibition is consistent with the hypothesis that free -NH2 groups are required for the attachment of ubiquitin prior to degradation in this system. Removal of an ammonium sulfate fraction from reticulocyte lysates produces a proteolytic system markedly different from the whole lysate [Speiser, S. & Etlinger, J. D. (1983) Proc. Natl Acad. Sci. USA 80, 3577-3580]. In this system both denatured and undenatured albumin and beta-lactoglobulin were degraded essentially independently of ATP. Methylation only slightly decreased the breakdown of denatured proteins, suggesting that they are not degraded via the ubiquitin pathway. A possible explanation of these results is that removal of the ammonium sulfate fraction unmasks an ATP-independent proteolytic system unrelated to the ubiquitin pathway.

Degradation of microinjected methylated and unmethylated proteins in hepatoma tissue culture cells.

Radioiodinated proteins were introduced into hepatoma tissue culture (HTC) cells by erythrocyte ghost-mediated microinjection, and their degradation was studied. 125I-bovine serum albumin and 125I-lysozyme were degraded with half-lives of about 7 and 11 h, respectively. The process was ATP-dependent. The breakdown of these proteins was not inhibited by the following inhibitors of lysosomal proteolysis: NH4Cl, methylamine, chloroquine, leupeptin, or antipain. Methylation of 94% of the amino groups of bovine serum albumin or 99% of the amino groups of lysozyme had little effect on the rates of their degradation in HTC cells. In contrast, methylation almost completely inhibited the ATP-dependent proteolysis of both proteins in reticulocyte lysates. Methylated bovine serum albumin was not detectably demethylated in HTC cells. It is concluded that in HTC cells, bovine serum albumin and lysozyme are degraded by a nonlysosomal pathway which differs from the ubiquitin-dependent proteolysis system of reticulocytes in that it does not require free amino groups.

Control of luciferase synthesis in a newly isolated strain of Photobacterium leiognathi.

In previous studies with luminous bacteria of all different species it has been reported that the synthesis of luciferase is autoinducible: during growth at low cell densities synthesis is effectively repressed while after induction, at higher cell densities, the rate of synthesis of enzyme is up to five times the growth rate. In this paper we report on newly isolated strains of Photobacterium leiognathi which show continued luciferase synthesis irrespective of the cell density. The specific synthesis rate may nevertheless differ from the rate of growth and depends on the luciferase content of the inoculated cells. A ratio of 1 was established for cells having a maximum luciferase content varying to a ratio of about 2 for cells that contained only 1% of the maximum.