Prehospital Analgesia With Intranasal Ketamine (PAIN-K): A Randomized Double-Blind Trial in Adults.

STUDY OBJECTIVE: We compare intranasal ketamine with intranasal placebo in providing pain reduction at 30 minutes when added to usual paramedic care with nitrous oxide. METHODS: This was a randomized double-blind study of out-of-hospital patients with acute pain who reported a verbal numeric rating scale (VNRS) pain score greater than or equal to 5. Exclusion criteria were younger than 18 years, known ketamine intolerance, nontraumatic chest pain, altered mental status, pregnancy, and nasal occlusion. Patients received usual paramedic care and were randomized to receive either intranasal ketamine or intranasal saline solution at 0.75 mg/kg. The primary outcome was the proportion of patients with VNRS score reduction greater than or equal to 2 at 30 minutes. Secondary outcomes were pain reduction at 15 minutes, patient-reported comfort, satisfaction scores, nitrous oxide consumption, and incidence of adverse events. RESULTS: One hundred twenty subjects were enrolled. Seventy-six percent of intranasal ketamine patients versus 41% of placebo patients reported a greater than or equal to 2-point VNRS reduction at 30 minutes (difference 35%; 95% confidence interval 17% to 51%). Median VNRS reduction at 15 minutes was 2.0 and 1.0 and at 30 minutes was 3.0 and 1.0 for ketamine and placebo, respectively. Improved comfort at 15 and 30 minutes was reported for 75% versus 57% and 61% versus 46% of ketamine and placebo patients, respectively. Sixty-two percent of patients (95% confidence interval 49% to 73%) versus 20% (95% confidence interval 12% to 32%) reported adverse events with ketamine and placebo, respectively. Adverse events were minor, with no patients requiring physical or medical intervention. CONCLUSION: Added to nitrous oxide, intranasal ketamine provides clinically significant pain reduction and improved comfort compared with intranasal placebo, with more minor adverse events.

Gains of Continuing Resuscitation in Refractory Out-of-hospital Cardiac Arrest: A Model-based Analysis to Identify Deaths Due to Intra-arrest Prognostication.

OBJECTIVE: Prognostication bias, in which a clinician predicts a negative outcome and terminates resuscitation (TR) thereby ensuring a poor outcome, is a rarely identified limitation of out-of-hospital cardiac arrest (OHCA) research. We sought to estimate the number of deaths due to intra-arrest prognostication in a cohort of OHCA's, and use this data to estimate the incremental benefit of continuing resuscitation. METHODS: This study examined a cohort of consecutive non-traumatic EMS-treated OHCAs from a provincial ambulance service, between 2007 and 2011 inclusive. We used Cox and logistic regression modeling, adjusting for Utstein covariates, to estimate the probability of ROSC, survival, and favorable neurological outcomes as a function of resuscitation time, and applied these models to estimate the number of missed survivors in those who had TR (prior to 20, 30, or 40 minutes). We determined the time juncture at which (1) the likelihood of survival fell below 1%, and (2) the proportion of survivors who had achieved ROSC exceeded 99%. RESULTS: Of 5674 adult EMS-treated cases, 46% achieved ROSC, and 12% survived. The median time of TR was 27.0 minutes (IQR 19.0-35.0). Continuing resuscitation until 40 minutes yielded an estimated 17 additional survivors (95% CI 13-21), 10 (95% CI 7-13) with favorable neurological outcomes. The probability of survival of those in refractory arrest decreased below 1% at 28 minutes (95% CI 24-30 minutes). At 36 minutes (95% CI 34-38 minutes) >99% of survivors had achieved ROSC. CONCLUSION: We identified possible deaths due to intra-arrest prognostication. Resuscitation should be continued for a minimum of 30 minutes in all patients, however for those with initial shockable rhythms 40 minutes appears to be warranted. Interventional trials and observational studies should standardize or adjust for duration of resuscitation prior to TR.

External Validation of the Universal Termination of Resuscitation Rule for Out-of-Hospital Cardiac Arrest in British Columbia.

STUDY OBJECTIVE: The Universal Termination of Resuscitation Rule (TOR Rule) was developed to identify out-of-hospital cardiac arrests eligible for field termination of resuscitation, avoiding futile transportation to the hospital. The validity of the rule in emergency medical services (EMS) systems that do not routinely transport out-of-hospital cardiac arrest patients to the hospital is unknown. We seek to validate the TOR Rule in British Columbia. METHODS: This study included consecutive, nontraumatic, adult, out-of-hospital cardiac arrests treated by EMS in British Columbia from April 2011 to September 2015. We excluded patients with active do-not-resuscitate orders and those with missing data. Following consensus guidelines, we examined the validity of the TOR Rule after 6 minutes of resuscitation (to approximate three 2-minute cycles of resuscitation). To ascertain rule performance at the different time junctures, we recalculated TOR Rule classification accuracy at subsequent 1-minute resuscitation increments. RESULTS: Of 6,994 consecutive, adult, EMS-treated, out-of-hospital cardiac arrests, overall survival was 15%. At 6 minutes of resuscitation, rule performance was sensitivity 0.72, specificity 0.91, positive predictive value 0.98, and negative predictive value 0.36. The TOR Rule recommended care termination for 4,367 patients (62%); of these, 92 survived to hospital discharge (false-positive rate 2.1%; 95% confidence interval 1.7% to 2.5%); however, this proportion steadily decreased with later application. The TOR Rule recommended continuation of resuscitation in 2,627 patients (38%); of these, 1,674 died (false-negative rate 64%; 95% confidence interval 62% to 66%). Compared with 6-minute application, test characteristics at 30 minutes demonstrated nearly perfect positive predictive value (1.0) and specificity (1.0) but a lower sensitivity (0.46) and negative predictive value (0.25). CONCLUSION: In this cohort of adult out-of-hospital cardiac arrest patients, the TOR Rule applied at 6 minutes falsely recommended care termination for 2.1% of patients; however, this decreased with later application. Systems using the TOR Rule to cease resuscitation in the field should consider rule application at points later than 6 minutes.

Population-based analysis of the effect of a comprehensive, systematic change in an emergency medical services resource allocation plan on 24-hour mortality.

BACKGROUND: Resource allocation planning for emergency medical services (EMS) systems determines appropriate resources including what paramedic qualification and how rapidly to respond to patients for optimal outcomes. The British Columbia Emergency Health Services implemented a revised response plan in 2013. METHODS: A pre- and post-methodology was used to evaluate the effect of the resource allocation plan revision on 24-hour mortality. All adult cases with evaluable outcome data (obtained through linked provincial health administrative data) were analyzed. Multivariable logistic regression was used to adjust for variations in other significant associated factors. Interrupted time series analysis was used to estimate immediate changes in level or trend of outcome after the start of the revised resource allocation plan implementation, while simultaneously controlling for pre-existing trends. RESULTS: The derived cohort comprised 562,546 cases (April 2012-March 2015). When adjusted for age, sex, urban/metro region, season, day, hour, and dispatch determinant, the probability of dying within 24 hours of an EMS call was 7% lower in the post-resource allocation plan-revision cohort (OR = 0.936; 95% CI: 0.886-0.989; p = 0.018). A subgroup analysis of immediately life-threatening cases demonstrated similar effect (OR = 0.890; 95% CI: 0.808-0.981; p = 0.019). Using time series analysis, the descending changes in overall 24-hour mortality trend and the 24-hour mortality trend in immediately life-threatening cases, were both statistically significant (p < 0.001). CONCLUSION: Comprehensive, evidence-informed reconstruction of a provincial EMS resource allocation plan is feasible. Despite change in crew level response and resource allocation, there was significant decrease in 24-hour mortality in this pan-provincial population-based cohort.

A Local Sensitivity Analysis of the Trial of Continuous or Interrupted Chest Compressions during Cardiopulmonary Resuscitation: Is a Local Protocol Change Required?

Objective The "Trial of Continuous (CCC) or Interrupted Chest Compressions (ICC) during Cardiopulmonary Resuscitation (CPR)" compared two CPR strategies for out-of-hospital cardiac arrest (OHCA). Although results were neutral, there was suggestion of benefit for ICC. However, nearly 50% of study patients had a protocol violation; regional variations may have played a role in protocol adherence and outcomes. We analyzed our British Colombia (BC) cohort to decide whether a protocol change from CCC to ICC was justified. Methods This was a post-hoc analysis of BC-enrolled study patients. The primary between-group comparison was favorable neurological outcome (modified Rankin scale ≤ 3) using intention-to-treat. Secondary analyses compared those treated per-protocol (adjusted) and the top compliant clusters (unadjusted). We classified protocol violations using a structured algorithm. We used logistic regression and computed the difference in probabilities using the marginal standardization method with bootstrapping to calculate confidence intervals. Results There were 3769 patients included, with a median age of 69 years (IQR: 56-80). There were protocol violations in 3.2% of those in the CCC group and 27% of those in the ICC group. In patients randomized to CCC or ICC, 11.2% and 10.8% (risk difference 0.42%; 95% CI -1.58, 2.41) had favorable neurological outcomes, respectively. In the per-protocol and top compliant clusters comparisons, risk differences were 0.25% (95% CI -1.70, 2.25) and 2.95% (95% CI -0.68, 6.58). Conclusion Our comparisons suggest that CCC may be the preferred strategy in our region and is likely not resulting in worse outcomes. Based on the original study and our local analysis, we found no compelling reasons to change our local strategy from CCC to ICC.

Trends in care processes and survival following prehospital resuscitation improvement initiatives for out-of-hospital cardiac arrest in British Columbia, 2006-2016.

BACKGROUND: British Columbia (BC) Emergency Health Services implemented a strategy to improve outcomes for out-of-hospital cardiac arrest (OHCA), focusing on paramedic-led high-quality on-scene resuscitation. We measured changes in care metrics and survival trends. METHODS: This was a post-hoc study of prospectively identified consecutive non-traumatic ambulance-treated adult OHCAs from 2006 to 2016 within BC's four metropolitan areas. The primary outcome was survival to hospital discharge; we also described available favourable neurological outcomes (mRS ≤3). We tested the significance of year-by-year trends in baseline characteristics, and calculated risk-adjusted survival rates using multivariable Poisson regression. RESULTS: We included 15 145 patients. In univariate analyses there were significant increases in bystander CPR, chest compression fraction, advanced life support attendance, duration of resuscitation until advanced airway placement, duration of resuscitation until termination, and overall scene time. There was a significant decrease in initial shockable rhythms, bystander witnessed arrests, and transports initiated prior to ROSC. Survival and the proportion of survivors with favourable neurological outcomes increased significantly. In adjusted analyses, there was an improvement in return of spontaneous circulation (risk-adjusted rate 41% in 2006 to 51% in 2016; adjusted rate ratio per year 1.02, 95% CI 1.01-1.02, p < 0.01 for trend) and survival at hospital discharge (risk-adjusted rate 8.6% in 2006 to 16% in 2016; adjusted rate ratio per year 1.05, 95% CI 1.04-1.06, p < 0.01 for trend). CONCLUSION: From 2006 to 2016 BC's provincial ambulance system prioritized paramedic-led on-scene resuscitation, during which time there were significant improvements in patient outcomes. Our data may assist other systems, providing a model for prehospital resuscitation quality improvement.

Prehospital sodium bicarbonate use could worsen long term survival with favorable neurological recovery among patients with out-of-hospital cardiac arrest.

BACKGROUND: Sodium bicarbonate (SB) is widely used for resuscitation in out-of- hospital cardiac arrest (OHCA); however, its effect on long term outcomes is unclear. METHODS: From 2005-2016, we prospectively conducted a province-wide population-based observational study including adult non-traumatic OHCA patients managed by paramedics. SB was administered by paramedics based on their clinical assessments. To examine the association of SB administration and survival and favorable neurological outcome to hospital discharge, defined as modified Rankin scale of 3 or less, we performed a multivariable logistic regression analysis: (1) within propensity score matched comparison groups, and; (2) within the full cohort with missing variables addressed by multiple imputation techniques. RESULTS: Of 15 601 OHCA patients, 13,865 were included in this study with 5165 (37.3%) managed with SB. In the SB treated group, 118 (2.3%) patients survived and 62 (1.2%) had favorable neurological outcomes to hospital discharge, compared to 1699 (19.8%) and 831 (10.6%) in the non-SB treated group, respectively. In the 1:1 propensity matched cohort including 5638 OHCA patients, SB was associated with decreased probability of outcomes (adjusted OR for survival: 0.64, 95% CI 0.45-0.91, and adjusted OR for favorable neurological outcome: 0.59, 95% CI 0.39-0.88, respectively). The association remained consistent in the multiply imputed cohort (adjusted OR 0.48, 95 CI 0.36-0.64, and adjusted OR 0.54, 95% CI 0.38-0.76, respectively). CONCLUSIONS: In OHCA patients, prehospital SB administration was associated with worse survival rate and neurological outcomes to hospital discharge.

A comprehensive regional clinical and educational ECPR protocol decreases time to ECMO in patients with refractory out-of-hospital cardiac arrest.

OBJECTIVE: Extracorporeal membrane oxygenation within CPR (ECPR) may improve survival for refractory out-of-hospital cardiac arrest (OHCA). We developed a prehospital, emergency department (ED), and hospital-based clinical and educational protocol to improve the key variable of time-to-ECPR (TTE). METHODS: In a single urban health region we involved key prehospital, clinical, and administrative stakeholders over a 2-year period, to develop a regional ECPR program with destination to a single urban tertiary care hospital. We developed clear and reproducible inclusion criteria and processes, including measures of program efficiency. We conducted seminars and teaching modules to paramedics and hospital-based clinicians including monthly simulator sessions, and performed detailed reviews of each treated case in the form of report cards. In this before-and-after study we compared patients with ECPR attempted prior to, and after, protocol implementation. The primary outcome was TTE, defined as the time of initial professional CPR to establishment of extracorporeal circulation. We compared the median TTE for patients in the two groups using the Wilcoxon signed rank test. RESULTS: Four patients were identified prior to the protocol and managed in an ad hoc basis; for nine patients the protocol was utilized. Overall favourable neurological outcomes among ECPR-treated patients were 27%. The median TTE was 136 minutes (IQR 98 - 196) in the pre-protocol group, and 60 minutes (IQR 49 - 81) minutes in the protocol group (p=0.0165). CONCLUSION: An organized clinical and educational protocol to initiate ECPR for patients with OHCA is feasible and significantly reduces the key benchmark of time-to-ECPR flows.

Reduction of Fasting Blood Glucose and Hemoglobin A1c Using Oral Aloe Vera: A Meta-Analysis.

PURPOSE: Diabetes mellitus is a global epidemic and one of the leading causes of morbidity and mortality. Additional medications that are novel, affordable, and efficacious are needed to treat this rampant disease. This meta-analysis was performed to ascertain the effectiveness of oral aloe vera consumption on the reduction of fasting blood glucose (FBG) and hemoglobin A1c (HbA1c). METHODS: PubMed, CINAHL, Natural Medicines Comprehensive Database, and Natural Standard databases were searched. Studies of aloe vera's effect on FBG, HbA1c, homeostasis model assessment-estimated insulin resistance (HOMA-IR), fasting serum insulin, fructosamine, and oral glucose tolerance test (OGTT) in prediabetic and diabetic populations were examined. After data extraction, the parameters of FBG and HbA1c had appropriate data for meta-analyses. Extracted data were verified and then analyzed by StatsDirect Statistical Software. Reductions of FBG and HbA1c were reported as the weighted mean differences from baseline, calculated by a random-effects model with 95% confidence intervals. Subgroup analyses to determine clinical and statistical heterogeneity were also performed. Publication bias was assessed by using the Egger bias statistic. RESULTS: Nine studies were included in the FBG parameter (n = 283); 5 of these studies included HbA1c data (n = 89). Aloe vera decreased FBG by 46.6 mg/dL (p < 0.0001) and HbA1c by 1.05% (p = 0.004). Significant reductions of both endpoints were maintained in all subgroup analyses. Additionally, the data suggest that patients with an FBG ≥200 mg/dL may see a greater benefit. A mean FBG reduction of 109.9 mg/dL was observed in this population (p ≤ 0.0001). The Egger statistic showed publication bias with FBG but not with HbA1c (p = 0.010 and p = 0.602, respectively). CONCLUSION: These results support the use of oral aloe vera for significantly reducing FBG (46.6 mg/dL) and HbA1c (1.05%). Further clinical studies that are more robust and better controlled are warranted to further explore these findings.