Michael N. Cocchi

Part 4: Advanced life support

The International Liaison Committee on Resuscitation (ILCOR) Advanced Life Support (ALS) Task Force performed detailed systematic reviews based on the recommendations of the Institute of Medicine of the National Academies1 and using the methodological approach proposed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Working Group.2 Questions to be addressed (using the PICO [population, intervention, comparator, outcome] format)3 were prioritized by ALS Task Force members (by voting). Prioritization criteria included awareness of significant new data and new controversies or questions about practice. Questions about topics no longer relevant to contemporary practice or where little new research has occurred were given lower priority. The ALS Task Force prioritized 42 PICO questions for review. With the assistance of information specialists, a detailed search for relevant articles was performed in each of 3 online databases (PubMed, Embase, and the Cochrane Library). By using detailed inclusion and exclusion criteria, articles were screened for further evaluation. The reviewers for each question created a reconciled risk of bias assessment for each of the included studies, using state-of-the-art tools: Cochrane for randomized controlled trials (RCTs),4 Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 for studies of diagnostic accuracy,5 and GRADE for observational studies that inform both therapy and prognosis questions.6 GRADE evidence profile tables7 were then created to facilitate an evaluation of the evidence in support of each of the critical and important outcomes. The quality of the evidence (or confidence in the estimate of the effect) was categorized as high, moderate, low, or very low,8 based on the study methodologies and the 5 core GRADE domains of risk of bias, inconsistency, indirectness, imprecision, and other considerations (including publication bias).9 These evidence profile tables were then used to create a …

Neurologic recovery after therapeutic hypothermia in patients with post-cardiac arrest myoclonus

Early myoclonus in comatose survivors of cardiac arrest, even when it is not myoclonic status epilepticus (MSE), is considered a sign of severe global brain ischemia and has been associated with high rates of mortality and poor neurologic outcomes. We report on three survivors of primary circulatory cardiac arrests who had good neurologic outcomes (two patients with a CPC score=1 and one patient with a CPC score=2) after mild therapeutic hypothermia, despite exhibiting massive myoclonus within the first 4h after return of spontaneous circulation. The concept that early myoclonus heralds a uniformly poor prognosis may need to be reconsidered in the era of post-cardiac arrest mild therapeutic hypothermia.

Thiamine deficiency in critically ill patients with sepsis.

OBJECTIVE The objective of the study was to determine the prevalence of absolute thiamine deficiency (TD) in critically ill patients with sepsis and to examine the association between thiamine levels and lactic acidosis. DESIGN This was a prospective, observational study. SETTING The setting was an urban, tertiary care center with approximately 50,000 emergency department visits per year and intensive care units numbering approximately 50 total beds. PATIENTS Thirty study patients admitted with clinical suspicion of infection and evidence of tissue hypoperfusion, as defined by a lactic acid level greater than 4 mmol/L or hypotension (systolic blood pressure <90 mm Hg) requiring vasopressor support, were enrolled. A control group of 30 patients presenting to the emergency department with minor emergencies was also enrolled. INTERVENTIONS There were no interventions. MEASUREMENTS AND MAIN RESULTS Plasma thiamine levels were measured at 0, 24, 48, 72, and 162 hours for patients in the study group. Absolute TD was defined as less than or equal to 9 nmol/L derived from established abnormal ranges per Quest laboratory. In the study group, 3 (10%) of 30 had absolute TD upon presentation; and an additional 3 patients (6/30, 20%) developed TD within 72 hours. None of the 30 controls (0/30, 0%) exhibited absolute TD. Of the vasopressor-dependent population, 7.7% (2/26) displayed TD on presentation. For the group overall, there was no correlation between thiamine and lactic acidosis. However, in patients without liver dysfunction, thiamine was statistically significantly negatively correlated with lactic acidosis (r = -.50; P = .02). The relationship between thiamine and lactic acidosis held after multivariable regression analysis controlling for age, sex, and comorbid disease (P < .02). CONCLUSIONS These preliminary findings indicate that critically ill patients may present with TD or develop this deficiency during their acute illness. We also identified a potential association between thiamine levels and lactic acidosis in patients without significant liver injury.

The development and implementation of cardiac arrest centers

In the last decade, many regionalized centers for the care of post-cardiac arrest patients (cardiac arrest centers) have all independently developed with a common goal of providing multi-disciplinary and organized care plans for this patient population. The American Heart Association recently issued support for regionalized and organized comprehensive care for post-arrest patients through a position paper as well as the 2010 American Heart Association BLS/ACLS guidelines. This paper outlines the formation, structure, and implementation of four cardiac arrest centers, and also discusses a statewide model of post-arrest center care. This paper may assist other potential clinical sites that are considering or actively developing cardiac arrest centers of their own.

Statin therapy is associated with decreased mortality in patients with infection.

OBJECTIVES The objective was to investigate the association between statin therapy and mortality in emergency department (ED) patients with suspected infection. METHODS A secondary analysis of a prospective, observational cohort study was conducted at an urban, academic ED with approximately 50,000 annual visits. Data were collected between December 2003 and September 2004. Inclusion criteria consisted of age > or = 18 years, clinical suspicion of infection, and hospital admission. Patients were divided by those receiving statin therapy and those not receiving statins while hospitalized. Medication data were collected from an inpatient pharmacy database. Comparisons were conducted with Fishers exact test or Wilcoxon rank sum test. To adjust for baseline differences, multivariable logistic regression analysis controlling for gender, severity of illness (Mortality in Emergency Department Sepsis [MEDS] score), Charlson Comorbidity Index, and duration of statin therapy was performed. RESULTS Of 2,132 patients with suspected infection, 2,036 (95%) had interpretable pharmacy data and were analyzed. The cohort had a median age of 61 years (interquartile range [IQR] = 46-78 years) and a mortality of 3.9% (95% confidence interval [CI] = 3.1% to 4.8%). Patients who received statins (n = 474) had a lower unadjusted crude mortality (1.9%; 95% CI = 0.6% to 3.3%) compared to those who did not (4.5%; 95% CI = 3.4% to 5.4%; p </= 0.01). When adjusting for gender, MEDS score, Charlson Comorbidity Index, and duration of statin therapy, the odds of death for statin patients was 0.27 (95% CI = 0.1 to 0.72; p < or = 0.01). CONCLUSIONS Patients who were admitted to the hospital with infection and received statin therapy while hospitalized had a significantly lower in-hospital mortality compared to patients who did not receive a statin.

Initial lactate and lactate change in post-cardiac arrest: a multicenter validation study.

Objective:Rate of lactate change is associated with in-hospital mortality in post-cardiac arrest patients. This association has not been validated in a prospective multicenter study. The objective of the current study was to determine the association between percent lactate change and outcomes in post-cardiac arrest patients. Design:Four-center prospective observational study conducted from June 2011 to March 2012. Setting:The National Post-Arrest Research Consortium is a clinical research network conducting research in post-cardiac arrest care. The network consists of four urban tertiary care teaching hospitals. Patients:Inclusion criteria consisted of adult out-of-hospital non-traumatic cardiac arrest patients who were comatose after return of spontaneous circulation. Interventions:None. Measurements and Main Results:The primary outcome was survival to hospital discharge, and secondary outcome was good neurologic outcome. We compared the absolute lactate levels and the differences in the percent lactate change over 24 hours between survivors and nonsurvivors and between subjects with good and bad neurologic outcomes. One hundred patients were analyzed. The median age was 63 years (interquartile range, 50–75) and 40% were female. Ninety-seven percent received therapeutic hypothermia, and overall survival was 46%. Survivors and patients with good neurologic outcome had lower lactate levels at 0, 12, and 24 hours (p< 0.01). In adjusted models, percent lactate decrease at 12 hours was greater in survivors (odds ratio, 2.2; 95% CI, 1.1–6.2) and in those with good neurologic outcome (odds ratio, 2.2; 95% CI, 1.1–4.4). Conclusion:Lower lactate levels at 0, 12, and 24 hours and greater percent decrease in lactate over the first 12 hours post cardiac arrest are associated with survival and good neurologic outcome.

Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study.

Objective:To determine if intravenous thiamine would reduce lactate in patients with septic shock. Design:Randomized, double-blind, placebo-controlled trial. Setting:Two US hospitals. Patients:Adult patients with septic shock and elevated (> 3 mmol/L) lactate between 2010 and 2014. Interventions:Thiamine 200 mg or matching placebo twice daily for 7 days or until hospital discharge. Measurements and Main Results:The primary outcome was lactate levels 24 hours after the first study dose. Of 715 patients meeting the inclusion criteria, 88 patients were enrolled and received study drug. There was no difference in the primary outcome of lactate levels at 24 hours after study start between the thiamine and placebo groups (median: 2.5 mmol/L [1.5, 3.4] vs. 2.6 mmol/L [1.6, 5.1], p = 0.40). There was no difference in secondary outcomes including time to shock reversal, severity of illness and mortality. 35% of the patients were thiamine deficient at baseline. In this predefined subgroup, those in the thiamine treatment group had statistically significantly lower lactate levels at 24 hours (median 2.1 mmol/L [1.4, 2.5] vs. 3.1 [1.9, 8.3], p = 0.03). There was a statistically significant decrease in mortality over time in those receiving thiamine in this subgroup (p = 0.047). Conclusion:Administration of thiamine did not improve lactate levels or other outcomes in the overall group of patients with septic shock and elevated lactate. In those with baseline thiamine deficiency, patients in the thiamine group had significantly lower lactate levels at 24 hours and a possible decrease in mortality over time.

Continuous neuromuscular blockade is associated with decreased mortality in post-cardiac arrest patients

AIM Neuromuscular blockade may improve outcomes in patients with acute respiratory distress syndrome. In post-cardiac arrest patients receiving therapeutic hypothermia, neuromuscular blockade is often used to prevent shivering. Our objective was to determine whether neuromuscular blockade is associated with improved outcomes after out-of-hospital cardiac arrest. METHODS A post hoc analysis of a prospective observational study of comatose adult (>18 years) out-of-hospital cardiac arrest at 4 tertiary cardiac arrest centers. The primary exposure of interest was neuromuscular blockade for 24h following return of spontaneous circulation and primary outcomes were in-hospital survival and functional status at hospital discharge. Secondary outcomes were evolution of oxygenation (PaO2:FiO2), and change in lactate. We tested the primary outcomes of in-hospital survival and neurologically intact survival with multivariable logistic regression. Secondary outcomes were tested with multivariable linear mixed-models. RESULTS A total of 111 patients were analyzed. In patients with 24h of sustained neuromuscular blockade, the crude survival rate was 14/18 (78%) compared to 38/93 (41%) in patients without sustained neuromuscular blockade (p=0.004). After multivariable adjustment, neuromuscular blockade was associated with survival (adjusted OR: 7.23, 95% CI: 1.56-33.38). There was a trend toward improved functional outcome with neuromuscular blockade (50% versus 28%; p=0.07). Sustained neuromuscular blockade was associated with improved lactate clearance (adjusted p=0.01). CONCLUSIONS We found that early neuromuscular blockade for a 24-h period is associated with an increased probability of survival. Secondarily, we found that early, sustained neuromuscular blockade is associated with improved lactate clearance.

Inadequacy of temperature and white blood cell count in predicting bacteremia in patients with suspected infection.

BACKGROUND Early treatment of sepsis in Emergency Department (ED) patients has lead to improved outcomes, making early identification of the disease essential. The presence of systemic inflammatory response criteria aids in recognition of infection, although the reliability of these markers is variable. STUDY OBJECTIVE This study aims to quantify the ability of abnormal temperature, white blood cell (WBC) count, and bandemia to identify bacteremia in ED patients with suspected infection. METHODS This was a post hoc analysis of data collected for a prospective, observational, cohort study. Consecutive adult (age ≥ 18 years) patients who presented to the ED of a tertiary care center between February 1, 2000 and February 1, 2001 and had blood cultures obtained in the ED or within 3 h of admission were enrolled. Patients with bacteremia were identified and charts were reviewed for presence of normal temperature (36.1-38°C/97-100.4°F), normal WBC (4-12 K/μL), and presence of bandemia (> 5% of WBC differential). RESULTS There were 3563 patients enrolled; 289 patients (8.1%) had positive blood cultures. Among patients with positive blood cultures, 33% had a normal body temperature and 52% had a normal WBC count. Bandemia was present in 80% of culture-positive patients with a normal temperature and 79% of culture-positive patients with a normal WBC count. Fifty-two (17.4%) patients with positive blood cultures had neither an abnormal temperature nor an abnormal WBC. CONCLUSION A significant percentage of ED patients with blood culture-proven bacteremia have a normal temperature and WBC count upon presentation. Bandemia may be a useful clue for identifying occult bacteremia.

Cannabinoid hyperemesis: a case series.

BACKGROUND Cannabinoid use is prevalent in the United States, with recent reports of increased usage among younger Americans. Traditionally, cannabinoids have been used recreationally or as antiemetics; however, recent reports suggest that chronic abuse can result in the paradoxical effect of a cyclic vomiting syndrome, termed cannabinoid hyperemesis. OBJECTIVE We report on this recently described clinical syndrome characterized by severe nausea and hyperemesis in the setting of chronic cannabinoid use. CASE REPORTS We report the cases of 3 patients who presented to two academic emergency departments (EDs) on multiple occasions with nausea and vomiting in the setting of chronic cannabinoid use. There were extensive medical evaluations and frequent inpatient hospital admissions before the diagnosis of cannabinoid hyperemesis was considered. CONCLUSION With the relatively high prevalence of cannabinoid use in the United States and increasing interest in the applications of marijuana for therapeutic purposes, this entity may be encountered in the ED. Cannabinoid hyperemesis should be considered in the differential diagnosis of patients presenting with similar symptoms.