Effect of intrathecal dexmedetomidine versus intravenous dexmedetomidine on subarachnoid anesthesia with hyperbaric bupivacaine.

BACKGROUND AND AIM: Alpha-2 agonists such as dexmedetomidine when given intravenously or intrathecally as an adjuvant potentiate subarachnoid anesthesia. We studied the difference in subarachnoid anesthesia when supplemented with either intrathecal or intravenous dexmedetomidine. MATERIAL AND METHODS: Seventy-five patients posted for lower limb and infraumbilical procedures were enrolled for a prospective, randomized, double-blind, placebo-controlled study and divided into three groups: Group B (n = 25) received intravenous 20 mL 0.9%N aCl over 10 min followed by intrathecal 2.4 mL 0.5%bupivacaine + 0.2 mL sterile water; Group BDexIT (n = 25) received intravenous 20 mL 0.9%N aCl over 10 min followed by intrathecal 2.4 mL 0.5%b upivacaine + 0.2 mL (5 µg) dexmedetomidine; Group BDexIV (n = 25) received intravenous dexmedetomidine 1 µg/kg in 20 mL 0.9%N aCl over 10 min followed by intrathecal 2.4 mL 0.5%b upivacaine + 0.2 mL sterile water. Onset and recovery from motor and sensory blockade, and sedation score were recorded. Onset of sensory and motor blockade was assessed using Kruskal-Wallis test, whereas 2-segment regression and recovery was analyzed using ANOVA and post hoc Tukey's test to determine difference between the three groups. P value <0.05 was considered statistically significant. RESULTS: Although onset of sensory and motor block was similar in the three groups, motor recovery (modified Bromage scale 1) and two-segment sensory regression was prolonged in Group BDexIT > Group BDexIV > Group B (P < 0.001). Patients in Group BDexIT and Group BDexIV were sedated but easily arousable. CONCLUSION: Intrathecal dexmedetomidine prolongs the effect of subarachnoid anesthesia with arousable sedation when compared with intravenous dexmedetomidine.

Autonomic Effects of Pulsed Field vs Thermal Ablation for Treating Atrial Fibrillation: Subanalysis of ADVENT.

BACKGROUND: Autonomic denervation is an ancillary phenomenon during thermal ablation of atrial fibrillation (AF), that may have synergistic effects on symptomatic improvement and long-term freedom from AF. Pulsed field ablation (PFA), a nonthermal ablation modality, was noninferior to thermal ablation in treating AF; however, PFA's relative myocardial selectivity may minimize autonomic effects. OBJECTIVES: This study sought to compare heart rate (HR) and heart rate variability (HRV) metrics as markers of autonomic function after ablation using PFA vs thermal ablation. METHODS: ADVENT (The FARAPULSE ADVENT PIVOTAL Trial PFA System vs SOC Ablation for Paroxysmal Atrial Fibrillation) was a randomized pivotal study comparing PFA (pentaspline catheter) with thermal ablation (radiofrequency [RF] or cryoballoon [CB]) for treating paroxysmal AF. Baseline HR was acquired from a pre-ablation 12-lead electrocardiogram, whereas follow-up HRs, as well as HRV (standard deviation of all normal to normal RR intervals, standard deviation of 5-minute average RR intervals) metrics, were derived from 72-hour Holter monitors at 6 and 12 months. RESULTS: This study included 379 paroxysmal AF patients undergoing PFA (n = 194) or thermal ablation (n = 185; n = 102 RF, n = 83 CB) completing 6- and 12-month Holter monitoring. Compared with PFA, thermal patients had significantly greater increases in HR from baseline to 6 months (ΔHR; 10.1 vs 5.9 beats/min; P = 0.02) and 12 months (ΔHR; 8.8 vs 5.2 beats/min; P = 0.03). This increase in HR at 6 and 12 months was similar between CB and RF (P = 0.94 and 0.83, respectively). HRV, both standard deviation of all normal to normal RR intervals and standard deviation of 5-minute average RR intervals, were significantly lower at both 6 and 12 months after thermal ablation compared with PFA (P < 0.01). CONCLUSIONS: PFA's effect on the autonomic nervous system was attenuated compared with thermal ablation. Whether this affects long-term freedom from AF or symptomatic bradycardia/pauses after AF ablation requires further study.

Diabetes and Risk of Sudden Death in Coronary Artery Disease Patients Without Severe Systolic Dysfunction.

OBJECTIVES: This study sought to determine the absolute and relative associations of diabetes mellitus (DM) and hemoglobin A1c (HbA1c) with sudden and/or arrhythmic death (SAD) versus other modes of death in patients with coronary artery disease (CAD) who do not qualify for implantable cardioverter-defibrillators. BACKGROUND: Patients with CAD and DM are at elevated risk for SAD; however, it is unclear whether these patients would benefit from implantable cardioverter-defibrillators given competing causes of death and/or whether HbA1c might augment SAD risk stratification. METHODS: In the PRE-DETERMINE study of 5,764 patients with CAD with left ventricular ejection fraction (LVEF) of >30% to 35%, competing risk analyses were used to compare the absolute and relative risks of SAD versus non-SAD by DM status and HbA1c level and to identify risk factors for SAD among 1,782 patients with DM. RESULTS: Over a median follow-up of 6.8 years, DM and HbA1c were significantly associated with SAD and non-SAD (P < 0.05 for all comparisons); however, the cumulative incidence of non-SAD (19.2%; 95% CI: 17.3%-21.2%) was almost 4 times higher than SAD (4.8%; 95% CI: 3.8%-5.9%) in DM patients. A similar pattern of absolute risk was observed across categories of HbA1c. In analyses limited to patients with DM, HbA1c was not associated with SAD, whereas low LVEF, atrial fibrillation, and electrocardiogram measurements were associated with higher SAD risk. CONCLUSIONS: In patients with CAD and LVEF of >30% to 35%, patients with DM and/or elevated HbA1c are at much higher absolute risk of dying from non-SAD than SAD. Clinical risk markers, and not HbA1c, were associated with SAD risk in patients with DM. (PRE-DETERMINE: Biologic Markers and MRI SCD Cohort Study; NCT01114269).

Caffeinated Beverage Intake, Dyspnea With Ticagrelor, and Cardiovascular Outcomes: Insights From the PEGASUS-TIMI 54 Trial.

Background A proposed cause of dyspnea induced by ticagrelor is an increase in adenosine blood levels. Because caffeine is an adenosine antagonist, it can potentially improve drug tolerability with regard to dyspnea. Furthermore, association between caffeine and cardiovascular events is of clinical interest. Methods and Results This prespecified analysis used data from the PEGASUS TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) trial, which randomized 21 162 patients with prior myocardial infarction to ticagrelor 60 mg or 90 mg or matching placebo (twice daily). Baseline caffeine intake in cups per week was prospectively collected for 9694 patients. Outcomes of interest included dyspnea, major adverse cardiovascular events (ie, the composite of cardiovascular death, myocardial infarction, or stroke), and arrhythmias. Dyspnea analyses considered the pooled ticagrelor group, whereas cardiovascular outcome analyses included patients from the 3 randomized arms. After adjustment, caffeine intake, compared with no intake, was not associated with lower rates of dyspnea in patients taking ticagrelor (adjusted hazard ratio (HR), 0.91; 95% CI, 0.76-1.10; P=0.34). There was no excess risk with caffeine for major adverse cardiovascular events (adjusted HR, 0.78; 95% CI, 0.63-0.98; P=0.031), sudden cardiac death (adjusted HR, 0.98; 95% CI, 0.57-1.70; P=0.95), or atrial fibrillation (adjusted odds ratio, 1.07; 95% CI, 0.56-2.04; P=0.84). Conclusions In patients taking ticagrelor for secondary prevention after myocardial infarction, caffeine intake at baseline was not associated with lower rates of dyspnea compared with no intake. Otherwise, caffeine appeared to be safe in this population, with no apparent increase in atherothrombotic events or clinically significant arrhythmias. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT01225562.

Open Access Publishing and Subsequent Citations Among Articles in Major Cardiovascular Journals.

BACKGROUND: While open access publishing among cardiovascular journals has increased in scope over the last decade, the relationship between open access and article citation volume remains unclear. METHODS: We evaluated the association between open access publishing and citation number in 2017 among 4 major cardiovascular journals. Articles indexed to PubMed with ≥5 citations were identified among the following journals: Circulation, European Heart Journal, Journal of the American College of Cardiology, and JAMA Cardiology. Multivariable Poisson regression models were adjusted for journal and article type. RESULTS: Of the 916 articles published in 2017, original investigations accounted for most articles (66.7%), followed by reviews (14.5%), guideline/scientific statements (8.4%), research letters (3.7%), viewpoints (3.7%), and editorials (2.9%). Among all articles, 43% (n = 391) were open access. Citation number was higher among open access articles compared with those with subscription access (14 [25th-75th percentile: 9-23] vs 11 [25th-75th percentile: 7-17]; P < .001). Open access status was significantly associated with higher number of citations after multivariable adjustment (ß coefficient: +0.42; 95% confidence interval, 0.38-0.45, P < .001). Open access articles had consistently higher citations compared with subscription access articles across the 3 most frequent article types. CONCLUSION: Among contemporary articles published in major cardiovascular journals, open access publishing accounted for over 40% of articles and was significantly associated with increased short-term citations. Further research is required to assess the variation in long-term citation rates based on open access publishing status.

Cangrelor in cardiogenic shock and after cardiopulmonary resuscitation: A global, multicenter, matched pair analysis with oral P2Y12 inhibition from the IABP-SHOCK II trial.

AIMS: Cangrelor has a potentially favorable pharmacodynamic profile in cardiogenic shock (CS). We aimed to evaluate the clinical course of CS patients undergoing percutaneous coronary intervention (PCI) treated with cangrelor. METHODS AND RESULTS: We retrospectively identified 136 CS patients treated with cangrelor. Patients were 1:1 matched to CS patients from the IABP-SHOCK II trial not receiving cangrelor by age, sex, cardiac arrest, type of myocardial infarction, culprit lesion, glycoprotein IIb/IIIa inhibitor, and oral P2Y12-receptor inhibitor and followed-up for 12 months. The study cohort consisted of 88 matched pairs. Thirty-day and 12-month mortality was 29.5% and 34.1% in cangrelor-treated patients and 36.4% and 47.1% in control group (P = 0.34 and P = 0.08, respectively). The rate of definite acute stent thrombosis was 2.3% in both groups. Moderate and severe bleeding events occurred in 21.6% in the cangrelor and 19.3% in the control group (P = 0.71). Patients treated with cangrelor more frequently experienced ≥1 TIMI flow grade improvement during PCI (92.9% vs. 81.2%, P = 0.02). CONCLUSION: Cangrelor treatment was associated with similar bleeding risk and significantly better TIMI flow improvement compared with oral P2Y12 inhibitors in CS patients undergoing PCI. The use of cangrelor in CS offers a potentially safe and effective antiplatelet option and should be evaluated in randomized trials.

The Current Landscape of Atrial Fibrillation and Atrial Flutter Clinical Trials: A Report of 348 Studies Registered With ClinicalTrials.gov.

OBJECTIVES: This analysis sought to systematically characterize trial-level patterns in atrial fibrillation/atrial flutter (AF/AFL) by using the ClinicalTrials.gov database. BACKGROUND: Despite an abundance of clinical trials in this field, there is a lack of high-level evidence guiding management of AF/AFL. METHODS: We queried all closed, phase II to IV interventional trials registered in the ClinicalTrials.gov database through October 2016 that enrolled patients known to have AF/AFL. Published trials were evaluated for methodological quality, using the 3-item Jadad scale (range: 0 to 5, where 5 = highest quality). RESULTS: The initial search yielded 465 uniquely registered studies, of which 348 directly studied AF/AFL. Of those studies, 173 (50%) were published, enrolling a median of 190 patients from a median of 15 sites. The volume of published trials increased over time (7% prior to 2008 vs. 41% from 2014 to 2016; p < 0.001 for trend). Of the completed trials, 29% remain unpublished. Industry sources accounted for most funding (54%). Recurrence of AF/AFL was the most common endpoint (45%), whereas rates of primary clinical endpoints were low (13%). The mean Jadad score of published trials of pharmacological approaches (n = 112) was 4.0 ± 1.4. Of the 61 AF/AFL trials involving ablation or device therapies, 69% were randomized, 28% were single-arm studies, and patient, proceduralist, and event-ascertainment blinding was used in 16%, 4%, and 44%, respectively. CONCLUSIONS: Contemporary trials of AF/AFL are often multicenter and modest in size. The primary study endpoint is commonly recurrence of arrhythmia, even in high-quality and late-phase trials. Although methodological quality is high in trials of pharmacologic approaches, trials of AF/AFL ablation and device therapies variably employ randomization and blinding.

Comparative Effects of Buprenorphine and Dexmedetomidine as Adjuvants to Bupivacaine Spinal Anaesthesia in Elderly Male Patients Undergoing Transurethral Resection of Prostrate: A Randomized Prospective Study.

BACKGROUND AND AIMS: Transurethral resection of the prostate is a commonly performed urological procedure in elderly men with spinal anaesthesia being the technique of choice. Use of low-dose spinal anesthetic drug with adjuvants is desirable. This study compares the sensorimotor effects of addition of buprenorphine or dexmedetomidine to low-dose bupivacaine. METHODS: Sixty patients were randomly allocated to three different groups. All received 1.8 mL 0.5% hyperbaric bupivacaine intrathecally. Sterile water (0.2 mL) or buprenorphine (60 µg) or dexmedetomidine (5 µg) was added to control group (Group C), buprenorphine group (Group B), and dexmedetomidine group (Group D), respectively. Time to the first analgesic request was the primary objective, and other objectives included the level of sensory-motor block, time to two-segment regression, time to S1 sensory regression and time to complete motor recovery. ANOVA and post hoc test were used for statistical analysis. The value of P < 0.05 was considered statistically significant. RESULTS: All sixty patients completed the study. Postoperative analgesia was not required in the first 24 h in a total of 10 (50%), 12 (60%) and 15 (75%) patients in groups C, B, and D, respectively. Time to S1 regression was 130 ± 46 min (Group C), 144 ± 51.3 min (Group B) and 164 ± 55.99 min (Group D), P = 0.117. Time to complete motor recovery was 177 ± 56.9 min (Group C), 236 ± 60 min (Group B) and 234 ± 61.71 min (Group D), P < 0.001. CONCLUSION: Addition of buprenorphine (60 µg) or dexmedetomidine (5 µg) to intrathecal bupivacaine for transurethral resection prolongs the time to the first analgesic request with comparable recovery profile.

Epidemiological profile of acute respiratory distress syndrome patients: A tertiary care experience.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is seen in critically ill patients. Its etiological spectrum in India is expected to be different from that seen in western countries due to the high prevalence of tropical infections. AIM: To study the epidemiological profile of ARDS patients. SETTING: A tertiary care hospital in Karnataka, India. MATERIALS AND METHODS: Retrospective analysis of 150 out of the 169 ARDS patients diagnosed during 2010-2012. Data collected included the clinical features and severity scoring parameters. RESULTS: The mean age of the study population was 42.92 ± 13.91 years. The causes of ARDS included pneumonia (n = 35, 23.3%), scrub typhus (n = 33, 22%), leptospirosis (n = 11, 7.3%), malaria (n = 6, 4%), influenza (H1N1) (n = 10, 6.7%), pulmonary tuberculosis (n = 2, 1.3%), dengue (n = 1, 0.7%), abdominal sepsis (n = 16, 10.7%), skin infection (n = 3, 2%), unknown cause of sepsis (n = 18, 12%), and nonseptic causes (n = 15, 10%). A total of 77 (51.3%) patients survived, 66 (44%) expired, and 7 (4.7%) were discharged against medical advice (AMA). Preexisting comorbidities (46) were present in 13 survivors, 19 nonsurvivors, and four discharged AMA. History of surgery prior to the onset of ARDS was present in one survivor, 13 nonsurvivors, and one discharge AMA. Mean Acute Physiology and Chronic Health Evaluation (APACHE) II, APACHE III, and Sequential Organ Failure Assessment scores in survivors were 9.06 ± 4.3, 49.22 ± 14, and 6.43 ± 2.5 and in nonsurvivors 21.11 ± 7, 86.45 ± 23.5, and 10.6 ± 10, respectively. CONCLUSION: The most common cause of ARDS in our study was pneumonia, but a large percentage of cases were due to the tropical infections. Preexisting comorbidity, surgery prior to the onset of ARDS, higher severity scores, and organ failure scores were more frequently observed among nonsurvivors than survivors.

Anemia and its association with clinical outcome in heart failure patients undergoing cardiac resynchronization therapy.

PURPOSE: Although a substantial proportion of patients with heart failure (HF) have anemia, there is a paucity of data evaluating the impact of anemia on clinical outcome in CRT patients. Our goal was to examine the ability of baseline hemoglobin (Hb) level and change in Hb level over time to predict clinical 2-year outcome and echocardiographic response to CRT. METHODS: Three hundred consecutive CRT patients (median 72 years [interquartile range (IQR) 16 years], 19% female) with baseline and follow-up hematological profiles available were examined. Baseline anemia was defined as Hb <12 g/dL in women and <13 g/dL in men, and patients were grouped into equal quartiles based on change in Hb. Two-year clinical outcome was determined using a composite endpoint that included HF hospitalization, left ventricular assist device (LVAD) placement, heart transplantation, and all-cause mortality. Echocardiographic reverse remodeling was examined at 6-month follow-up. RESULTS: One hundred fifty-one anemic patients were compared to 149 non-anemic patients. Changes in left ventricular dimensions and ejection fraction were similar for both groups. Univariate predictors of 2-year clinical outcome included baseline creatinine level, diuretic usage, and anemia; in multivariable regression, baseline anemia was an independent predictor for outcome (hazard ratio [HR] 1.79, 95% confidence interval [CI] [1.22-2.63], p = 0.003). The quartile with the most negative change in Hb concentration over time (≤-1.00 g/dL) had poorer event-free 2-year survival (HR 1.84, CI [1.13-3.00], p = 0.014). CONCLUSIONS: Baseline anemia and early postimplantation decline in Hb levels are associated with a worse 2-year prognosis in CRT patients, even though the magnitude of left ventricular reverse remodeling is similar compared to non-anemic patients.

Comparison of intubating conditions following administration of low-dose rocuronium or succinylcholine in adults: A randomized double blind study.

CONTEXT: Though rocuronium has a rapid onset of neuromuscular blockade like succinylcholine without the latter's adverse effects, its use is limited due to its prolonged action. AIM: Aim was to evaluate whether reducing the intubating dose of rocuronium shortens its duration of action, yet provides clinically acceptable intubating conditions. SETTINGS AND DESIGN: tt was a prospective, randomized, and double blind trial. MATERIALS AND METHODS: 100 American Society of Anaesthesiologists Physical Status (ASAPS) I or II patients aged between 18-65 years scheduled for elective surgery were randomly allotted one of the four rocuronium groups (rocuronium dose of 0.3 mg/kg intubated at 60 s or at 90 s, rocuronium 0.6 mg/kg intubated at 60 s or at 90 s) orsuccinylcholine group (succinylcholine 1.0 mg/kg intubated at 60 s) and intubating conditions were assessed with: Ease of laryngoscopy, vocal cord position, and reaction to insertion of tracheal tube and cuff inflation. STATISTICAL ANALYSIS: Statistical tests used were analysis of variance (ANOVA), Chi-Square test, Repeated measures of ANOVA and Mann-Whitney U test. RESULTS: Rocuronium in dosage of 0.3 mg/kg gaveclinically acceptable intubating conditions in 35% and 60% subjects at 60 s or 90 s, respectively, whereas in dosage of 0.6 mg/kg, intubating conditions were acceptable in 80% and 100% subjects intubated at 60 s and 90 s. CONCLUSION: Rocuronium in dose of 0.3 mg/kg does not give clinically acceptable intubating conditions at 60 or 90 s but has shorter duration of action. Rocuronium in dose of 0.6 mg/kg gives clinically acceptable intubating conditions at 60 or 90 s, comparable to succinylcholine 1 mg/kg.

Tongue traction is as effective as jaw lift maneuver for Trachlight-guided orotracheal intubation.

OBJECTIVE: The jaw lift maneuver has been traditionally used to facilitate Trachlight-guided orotracheal intubation. The aim of this study was to compare the jaw lift maneuver with another potentially useful maneuver, tongue traction, for facilitating Trachlight-guided orotracheal intubation. METHODS: This study was prospective and randomized in design. A single experienced investigator performed Trachlight-guided orotracheal intubations in 100 adult patients with clinically normal airways undergoing elective surgeries under general anesthesia with paralysis. Patients were divided into two groups: Group J (jaw lift); and Group T (tongue traction using a padded artery forceps). Three parameters were recorded: search time (device insertion to midline glow); time to intubate (device insertion to glow at suprasternal notch); and time to confirm (device insertion to confirmation of placement by capnography). RESULTS: All patients were intubated successfully using the Trachlight. Only one patient in Group J required more than two attempts for successful intubation. First and second attempt success rates were, respectively, 86% and 98% in Group J, and 92% and 100% in Group T. Mean search time, time to intubate and time to confirm were comparable: 6.36 ± 4.20 seconds, 11.23 ± 6.69 seconds and 21.59 ± 7.69 seconds, respectively, in Group J, and 6.81 ± 4.53 seconds, 10.79 ± 6.02 seconds and 22.80 ± 7.85 seconds, respectively, in Group T. CONCLUSION: The tongue traction maneuver is as good as the jaw lift maneuver with regard to the success rate and time taken for Trachlight-guided orotracheal intubation.