Alan C. Heffner

The effect of a quantitative resuscitation strategy on mortality in patients with sepsis: A meta-analysis

Objective:Quantitative resuscitation consists of structured cardiovascular intervention targeting predefined hemodynamic end points. We sought to measure the treatment effect of quantitative resuscitation on mortality from sepsis. Data Sources:We conducted a systematic review of the Cochrane Library, MEDLINE, EMBASE, CINAHL, conference proceedings, clinical practice guidelines, and other sources using a comprehensive strategy. Study Selection:We identified randomized control trials comparing quantitative resuscitation with standard resuscitation in adult patients who were diagnosed with sepsis using standard criteria. The primary outcome variable was mortality. Data Abstraction:Three authors independently extracted data and assessed study quality using standardized instruments; consensus was reached by conference. Preplanned subgroup analysis required studies to be categorized based on early (at the time of diagnosis) vs. late resuscitation implementation. We used the chi-square test and I2 to assess for statistical heterogeneity (p < 0.10, I2 > 25%). The primary analysis was based on the random effects model to produce pooled odds ratios with 95% confidence intervals. Results:The search yielded 29 potential publications; nine studies were included in the final analysis, providing a sample of 1001 patients. The combined results demonstrate a decrease in mortality (odds ratio 0.64, 95% confidence interval 0.43–0.96); however, there was statistically significant heterogeneity (p = 0.07, I2 = 45%). Among the early quantitative resuscitation studies (n = 6) there was minimal heterogeneity (p = 0.40, I2 = 2.4%) and a significant decrease in mortality (odds ratio 0.50, 95% confidence interval 0.37–0.69). The late quantitative resuscitation studies (n = 3) demonstrated no significant effect on mortality (odds ratio 1.16, 95% confidence interval 0.60–2.22). Conclusion:This meta-analysis found that applying an early quantitative resuscitation strategy to patients with sepsis imparts a significant reduction in mortality.

Part 10: Special Circumstances of Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

This Part of the 2015 American Heart Association (AHA) Guidelines Update for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) addresses cardiac arrest in situations that require special treatments or procedures other than those provided during basic life support (BLS) and advanced cardiovascular life support (ACLS). This Part summarizes recommendations for the management of resuscitation in several critical situations, including cardiac arrest associated with pregnancy (Part 10.1), pulmonary embolism (PE) (10.2), and opioid-associated resuscitative emergencies, with or without cardiac arrest (10.3). Part 10.4 provides recommendations on intravenous lipid emulsion (ILE) therapy, an emerging therapy for cardiac arrest due to drug intoxication. Finally, updated guidance for the management of cardiac arrest during percutaneous coronary intervention (PCI) is presented in Part 10.5. A table of all recommendations made in this 2015 Guidelines Update as well as those made in the 2010 Guidelines is contained in the Appendix. The special situations of resuscitation section (Part 12) of the 2010 AHA Guidelines for CPR and ECC 1 covered 15 distinct topic areas. The following topics were last updated in 2010: Additional information about drowning is presented in Part 5 of this publication, “Adult Basic Life Support and Cardiopulmonary Resuscitation Quality.” The recommendations in this 2015 Guidelines Update are based on an extensive evidence review process that was begun by the International Liaison Committee on Resuscitation (ILCOR) with the publication of the ILCOR 2010 International Consensus on CPR and ECC Science With Treatment …

Outcomes of Patients Undergoing Early Sepsis Resuscitation for Cryptic Shock Compared with Overt Shock

INTRODUCTION We sought to compare the outcomes of patients with cryptic versus overt shock treated with an emergency department (ED) based early sepsis resuscitation protocol. METHODS Pre-planned secondary analysis of a large, multicenter ED-based randomized controlled trial of early sepsis resuscitation. All subjects were treated with a quantitative resuscitation protocol in the ED targeting 3 physiological variables: central venous pressure, mean arterial pressure and either central venous oxygen saturation or lactate clearance. The study protocol was continued until all endpoints were achieved or a maximum of 6h. Outcomes data of patients who were enrolled with a lactate ≥ 4mmol/L and normotension (cryptic shock) were compared to those enrolled with sustained hypotension after fluid challenge (overt shock). The primary outcome was in-hospital mortality. RESULTS A total of 300 subjects were enrolled, 53 in the cryptic shock group and 247 in the overt shock group. The demographics and baseline characteristics were similar between the groups. The primary endpoint of in-hospital mortality was observed in 11/53 (20%, 95% CI 11-34) in the cryptic shock group and 48/247 (19%, 95% CI 15-25) in the overt shock group, difference of 1% (95% CI -10 to 14; log rank test p=0.81). CONCLUSION Severe sepsis with cryptic shock carries a mortality rate not significantly different from that of overt septic shock. These data suggest the need for early aggressive screening for and treatment of patients with an elevated serum lactate in the absence of hypotension.

Whole Blood Lactate Kinetics in Patients Undergoing Quantitative Resuscitation for Severe Sepsis and Septic Shock

BACKGROUND We sought to compare the association of whole-blood lactate kinetics with survival in patients with septic shock undergoing early quantitative resuscitation. METHODS This was a preplanned analysis of a multicenter, ED-based, randomized, controlled trial of early sepsis resuscitation. Inclusion criteria were suspected infection, two or more systemic inflammation criteria, either systolic BP< 90 mm Hg after a fluid bolus or lactate level > 4 mM, two serial lactate measurements, and an initial lactate level > 2.0 mM. We calculated the relative lactate clearance, rate of lactate clearance, and occurrence of early lactate normalization (decline to < 2.0 mM in the first 6 h). Area under the receiver operating characteristic curve (AUC) and multivariate logistic regression were used to determine the lactate kinetic parameters that were the strongest predictors of survival. RESULTS The analysis included 187 patients, of whom 36% (n = 68) normalized their lactate level. Overall survival was 76.5% (143 of 187 patients), and the AUC of initial lactate to predict survival was 0.64. The AUCs for relative lactate clearance and lactate clearance rate were 0.67 and 0.58, respectively. Lactate normalization was the strongest predictor of survival (adjusted OR, 5.2; 95% CI, 1.7-15.8), followed by lactate clearance ≥ 50% (OR, 4.0; 95% CI, 1.6-10.0). Lactate clearance ≥ 10% (OR, 1.6; 95% CI, 0.6-4.4) was not a significant independent predictor in this cohort. CONCLUSIONS In patients in the ED with a sepsis diagnosis, early lactate normalization during the first 6 h of resuscitation was the strongest independent predictor of survival and was superior to other measures of lactate kinetics. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT00372502; URL: clinicaltrials.gov.

Prognostic Value and Agreement of Achieving Lactate Clearance or Central Venous Oxygen Saturation Goals During Early Sepsis Resuscitation

OBJECTIVES Lactate clearance (LC) and central venous oxygen saturation (ScvO(2)) have been proposed as goals of early sepsis resuscitation. The authors sought to determine the agreement and prognostic value of achieving ScvO(2) or LC goals in septic shock patients undergoing emergency department (ED)-based early resuscitation. METHODS This was a preplanned analysis of a multicenter ED randomized controlled trial of early sepsis resuscitation targeting three variables: central venous pressure, mean arterial pressure, and either ScvO(2) or LC. Inclusion criteria included suspected infection, two or more systemic inflammation criteria, and either systolic blood pressure of <90 mm Hg after intravenous fluid bolus or lactate level of >4 mmol/L. Both ScvO(2) and LC were measured simultaneously. The ScvO(2) goal was defined as ≥70%. Lactate was measured at enrollment and every 2 hours until the goal was reached or up to 6 hours. LC goal was defined as a decrease of ≥10% from initial measurement. The primary outcome was in-hospital mortality. RESULTS A total of 203 subjects were included, with an overall mortality of 19.7%. Achievement of the ScvO(2) goal only was associated with a mortality rate of 41% (9/22), while achievement of the LC goal only was associated with a mortality rate of 8% (2/25; proportion difference = 33%; 95% confidence interval [CI] = 9% to 55%). No agreement was found between goal achievement (κ = -0.02), and exact test for matched pairs demonstrated no significant difference between discordant pairs (p = 0.78). CONCLUSIONS No agreement was found between LC and ScvO(2) goal achievement in early sepsis resuscitation. Achievement of a ScvO(2) ≥ 70% without LC ≥ 10% was more strongly associated with mortality than achievement of LC ≥ 10% with failure to achieve ScvO(2) ≥ 70%.

Etiology of Illness in Patients with Severe Sepsis Admitted to the Hospital from the Emergency Department

BACKGROUND Patients identified with sepsis in the emergency department often are treated on the basis of the presumption of infection; however, various noninfectious conditions that require specific treatments have clinical presentations very similar to that of sepsis. Our aim was to describe the etiology of illness in patients identified and treated for severe sepsis in the emergency department. METHODS We conducted a prospective observational study of patients treated with goal-directed resuscitation for severe sepsis in the emergency department. Inclusion criteria were suspected infection, 2 or more criteria for systemic inflammation, and evidence of hypoperfusion. Exclusion criteria were age of <18 years and the need for immediate surgery. Clinical data on eligible patients were prospectively collected for 2 years. Blinded observers used a priori definitions to determine the final cause of hospitalization. RESULTS In total, 211 patients were enrolled; 95 (45%) had positive culture results, and 116 (55%) had negative culture results. The overall mortality rate was 19%. Patients with positive culture results were more likely to have indwelling vascular lines (P = .03), be residents of nursing homes (P = .04), and have a shorter time to administration of antibiotics in the emergency department (83 vs 97 min; P = .03). Of patients with negative culture results, 44% had clinical infections, 8% had atypical infections, 32% had noninfectious mimics, and 16% had an illness of indeterminate etiology. CONCLUSION In this study, we found that >50% of patients identified and treated for severe sepsis in the emergency department had negative culture results. Of patients identified with a sepsis syndrome at presentation, 18% had a noninfectious diagnosis that mimicked sepsis, and the clinical characteristics of these patients were similar to those of patients with culture-positive sepsis.

Successful outcome utilizing hypothermia after cardiac arrest in pregnancy: a case report.

Background:To date, pregnancy has been considered a contraindication to the use of therapeutic hypothermia after cardiac arrest. Case:We present the case of a 35-yr-old woman, 13 wks pregnant, who had a witnessed out-of-hospital ventricular fibrillation cardiac arrest. She was resuscitated by prehospital personnel yet remained comatose at arrival to the hospital. Therapeutic cooling (33°C) was initiated for 24 hrs, and she was discharged home with mild neurologic deficit (Cerebral Performance Category 2) on hospital day 6. The infant was delivered via cesarean section at 39 wks’ gestation. Apgar scores were 8 and 9, and neurodevelopmental testing was appropriate for age at birth and at 2 months. Conclusion:This is the first case of therapeutic hypothermia applied to postarrest care of a pregnant woman followed by a successful delivery. This therapy should be considered in pregnant patients with cardiac arrest.

Predictors of the complication of postintubation hypotension during emergency airway management

OBJECTIVE Arterial hypotension is a recognized complication of emergency intubation that is independently associated with increased morbidity and mortality. Our aim was to identify factors associated with postintubation hypotension after emergency intubation. METHODS Retrospective cohort study of tracheal intubations performed in a large, urban emergency department over a 1-year period. Patients were included if they were older than 17 years and had no systolic blood pressure measurements below 90 mm Hg for 30 consecutive minutes before intubation. Patients were analyzed in 2 groups, those with postintubation hypotension (PIH), defined as any recorded systolic blood pressure less than 90 mm Hg within 60 minutes of intubation, and those with no PIH. Multiple logistic regression modeling was used to define predictors of PIH. RESULTS A total 465 patients underwent emergency intubation during the study period, and 300 met inclusion criteria for this study. Postintubation hypotension occurred in 66 (22%) of 300 patients, and these patients experienced significantly higher in-hospital mortality (35% vs 20%; odds ratio [OR] 2.1; 95% confidence interval [CI], 1.2-3.9). Multiple logistic regression analysis demonstrated that preintubation shock index (SI), chronic renal disease, intubation for acute respiratory failure, and age were independently associated with PIH. Of these, SI was the most strongly associated factor (OR, 55; 95% CI, 13-232). Receiver operating characteristic plot showed optimized SI 0.8 or higher predicting PIH with 67% sensitivity and 80% specificity. Rapid sequence intubation paralysis was associated with a lower incidence of PIH (OR, 0.04; 95% CI, 0.003-0.4). CONCLUSIONS Preintubation and peri-intubation factors predict the complication of PIH. Elevated SI strongly and independently forewarned of cardiovascular deterioration after emergency intubation with pre-RSI SI 0.8 or higher as the optimal threshold to identify patients at risk.

Incidence and factors associated with cardiac arrest complicating emergency airway management.

OBJECTIVE Cardiac arrest (CA) is a rare but recognized complication of emergency airway management. Our aim was to measure the incidence of peri-intubation CA during emergency intubation and identify factors associated with this complication. METHODS Retrospective cohort study of emergency endotracheal intubations performed in a large, urban emergency department over a one-year period. Patients were included if they were >18 years old and not in CA prior to intubation. Multiple logistic regression modeling was used to define factors independently associated with CA. RESULTS A total 542 patients underwent emergency intubation during the study period and 410 met inclusion criteria for this study. CA occurred in 17/410 (4.2%) at a median of 6 min post-intubation. Nearly two-thirds of CA events occurred within 10 min of drug induction; early peri-intubation CA rate 2.4% (95% CI: 1.3-4.5%). Pulseless electrical activity was the initial rhythm in the majority of cases. More than half of CA events were successfully resuscitated but CA was associated with increased odds of hospital death (OR 14.8; 95% CI: 4.2-52). Pre-intubation hemodynamic and oximetry variables were associated with CA. CA was more common in patients experiencing pre intubation hypotension (12% vs 3%; p<0.002). Pre RSI shock index (SI) and weight were independently associated with CA. CONCLUSIONS In this series, 1 in 25 emergency intubations was associated with the complication of CA. Peri-intubation CA is associated with increased mortality. Pre-intubation patient characteristics are associated with this complication.

The association between intra-arrest therapeutic hypothermia and return of spontaneous circulation among individuals experiencing out of hospital cardiac arrest

INTRODUCTION Therapeutic hypothermia has been shown to improve both mortality and neurologic outcomes following pulseless ventricular tachycardia and fibrillation. Animal data suggest intra-arrest induction of therapeutic hypothermia (IATH) improves frequency of return of spontaneous circulation (ROSC). Our objective was to evaluate the association between IATH and ROSC. METHODS This was a retrospective analysis of individuals experiencing non-traumatic cardiac arrest in a large metropolitan area during a 12-month period. Six months into the study a prehospital IATH protocol was instituted whereby patients received 2000ml of 4°C normal saline directly after obtaining IV/IO access. The main outcome variables were prehospital ROSC, survival to admission, and to discharge. A secondary analysis was conducted to assess the relationship between the quantity of cold saline infused and the likelihood of prehospital ROSC. RESULTS 551 patients met inclusion criteria with all the elements available for data analysis. Rates of prehospital ROSC were 36.5% versus 26.9% (OR 1.83; 95% CI 1.19-2.81) in patients who received IATH versus normothermic resuscitation respectively. While the frequency of survival to hospital admission and discharge were increased among those receiving IATH, the differences did not reach statistical significance. The secondary analysis found a linear association between the amount of cold saline infused and the likelihood of prehospital ROSC. CONCLUSION The infusion of 4°C normal saline during the intra-arrest period may improve rate of ROSC even at low fluid volumes. Further study is required to determine if intra-arrest cooling has a beneficial effect on rates of ROSC, mortality, and neurologic function.