HHS Public Access Author manuscript Author Manuscript
Shock. Author manuscript; available in PMC 2017 June 01. Published in final edited form as: Shock. 2016 June ; 45(6): 613–619. doi:10.1097/SHK.0000000000000554.
HEMODYNAMIC RESUSCITATION CHARACTERISTICS ASSOCIATED WITH IMPROVED SURVIVAL AND SHOCK RESOLUTION AFTER CARDIAC ARREST
Author Manuscript
Jonathan A. Janiczek*, Daniel G. Winger†, Patrick Coppler‡,§, Alexa R. Sabedra*, Holt Murray§, Michael R. Pinsky§, Jon C. Rittenberger**, Joshua C. Reynolds††, and Cameron Dezfulian‡,§,‡‡ *School
of Medicine, University of Pittsburgh, Pittsburgh, PA
†Clinical ‡Safar
and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA
Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA
§Department
of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA
**Department
of Emergency Medicine, University of Pittsburgh, Pittsburgh, PA
††Department
of Emergency Medicine, Michigan State University College of Human Medicine, Grand Rapids, MI ‡‡Vascular
Medicine Institute, University of Pittsburgh, Pittsburgh, PA
Author Manuscript
Abstract Purpose—To determine which strategy of early post-cardiac arrest hemodynamic resuscitation was associated with best clinical outcomes. We hypothesized that higher mean arterial pressure (MAP) achieved using IV fluids over vasopressors would yield better outcomes.
Author Manuscript
Methods—Retrospective cohort study of post-cardiac arrest patients between March 2011 and June 2012. Patients successfully resuscitated from cardiac arrest, admitted to an ICU and surviving at least 24 hours were included. Patients missing data for >2 hours after ROSC were excluded. The institutional standard for post-resuscitation MAP was ≥65 mmHg with no guidelines on how MAP was supported. We examined the association between early (6h) average MAP, vasopressor use summarized as cumulative vasopressor index (CVI) and fluid intake with outcomes including survival to discharge, favorable neurologic outcome based on Cerebral Performance Category (CPC) 1 or 2, and the surrogate outcome measure of lactate clearance using Pearson correlation and multivariable regression.
Address Correspondence to: Cameron Dezfulian, MD, Safar Center for Resuscitation Research, 206B Hill Building, 3434 Fifth Avenue, Pittsburgh, PA 15215, P: (412) 383-3128, F: (412) 383-1080, [email protected]. Conflicts of Interest: Janiczek: No conflicts; Winger: No conflicts; Sabedra: No conflicts; Dezfulian: No conflicts; The remaining authors have no disclosures. This project was completed at the University of Pittsburgh Medical Center: Mercy Hospital
Janiczek et al.
Page 2
Author Manuscript
Results—Of 118 patients, 55 (46%) survived to hospital discharge, 21 (18%) with favorable neurologic outcome. Higher 6h mean CVI was independently associated with worsened survival (OR 0.67; 95% CI 0.53, 0.85; p = 0.001). Resuscitation subgroups receiving higher than median vasopressors had worsened survival to hospital discharge regardless of fluid intake. In addition, higher MAP-6h correlated with increased lactate clearance (r=0.29; p= 0.011) Conclusions—Early post-ROSC hemodynamic resuscitation achieving higher MAP using fluid preferentially over vasopressors is associated with improved survival to hospital discharge as well as better lactate clearance. Keywords Cardiac Arrest; Shock; Resuscitation; Post-Cardiac Arrest Syndrome; Hemodynamics; Vasopressors; Fluid Administration
Author Manuscript
Introduction
Author Manuscript
Shock, a component of the post-cardiac arrest syndrome, is prevalent after resuscitation from cardiac arrest (1). This state of hemodynamic compromise often persists after return of spontaneous circulation (ROSC), and is associated with both increased in-hospital mortality and diminished functional outcome (2). This post-ROSC shock state may be secondary to myocardial dysfunction (2-4), a sepsis-like state (5), or both. Prior reports have noted an association between vasopressor use and mortality (1, 6, 7), even though higher blood pressure is also associated with improved outcomes (6). While some post-ROSC patients preserve adequate mean arterial pressure (MAP) without any hemodynamic intervention, many require significant resuscitation to achieve an appropriate MAP. It is unknown whether volume resuscitation or vasopressor administration is preferable for the shock state postROSC.
Author Manuscript
After ROSC, hemodynamic dysfunction is the major extracerebral injury associated with inhospital mortality (1). Given the parallels between cardiac arrest and sepsis (cytokine storm and myocardial dysfunction)(5), the International Liaison Committee on Resuscitation (ILCOR) and American Heart Association (AHA) have adopted similar goal-directed hemodynamic treatment recommendations as those used for sepsis (8) but little direct evidence supports MAP targets or the optimal means to achieve MAP (9). Improved outcomes have been noted with MAP of 65-75 mmHg (10), 80-100 mmHg (11), and >100 mmHg (12) compared to historical controls with lower MAP. However, the ideal MAP after ROSC is unknown, and hemodynamic management is rarely explicitly defined in postresuscitation care observational studies (13). Optimization of cardiac output using fluids may improves tissue perfusion (14) over merely achieving MAP targets using vasopressors. This leaves considerable uncertainty surrounding the optimal post-cardiac arrest resuscitation strategy. To better define the various strategies for early post-ROSC resuscitation, we ascertained MAP, the volume of resuscitative fluid used, and the amount of vasopressor used for a cohort of post-cardiac arrest patients at our institution. We then tested the associations between resuscitation strategy and clinical outcomes, and in a subset examined the
Shock. Author manuscript; available in PMC 2017 June 01.
Janiczek et al.
Page 3
Author Manuscript
association with lactate clearance (7, 15-17). We hypothesized that achieving higher MAP using volume resuscitation preferentially to vasopressors would be associated with improved outcomes which may also manifest as faster lactate clearance.
Materials and Methods Data from all patients at UPMC Mercy Hospital who received chest compressions or defibrillation, either in the hospital or prior to arrival, are entered into a quality improvement (QI) registry. The University of Pittsburgh Institutional Review Board approved retrospective analysis of this data as exempt and waived the requirement for informed consent to permit acquisition of additional data to address our study hypotheses. Study Setting and Population
Author Manuscript Author Manuscript
Data are from a single university-affiliated hospital with 59 critical care beds staffed by a single intensivist group providing 24/7 coverage. During the study period the institutional target for post-resuscitation MAP was ≥65 mmHg. No protocol existed to assess volume status or to direct fluid intake vs. vasopressors to achieve goal MAP. Hypothermia (target temperature 33°C) was provided for 24h using intravascular cooling (Thermoguard XP, Zoll, Chelmsford, MA) to all comatose patients regardless of presenting rhythm. EEG use was at the discretion of the provider but is only available for episodic not continuous monitoring and from quality assurance data is generally used in ~50% of comatose patients at days 2-3. There are no institutional guidelines on neuroprognostication and this is left to the judgement of the critical care provider. Sedation is targeted in all critically ill patients to Riker 3-4 with occasional rare exceptions. Our ICUs employ daily sedation interruptions to minimize over-sedation. Recently we reported that for cardiac arrest patients admitted to this center during a time period inclusive of the study dates (18) the rate of survival to discharge was 41% and the rate of good neurologic outcome was 19%. Study Design This retrospective cohort study included all adult (age ≥18 years) patients successfully resuscitated from out of hospital cardiac arrest (OHCA) or in hospital cardiac arrest (IHCA) from March, 2011 to June, 2012 and admitted to the ICU. We excluded patients who did not survive 24 hours beyond hospital admission. Most of these excluded early deaths resulted from limitation of care (withdrawal of life support or limited resuscitation), which significantly impacted the aggressiveness of early resuscitation. Study Definitions and Outcome Measures
Author Manuscript
We collected vital signs, vasopressor and inotrope infusion rates, fluid intake, output and balance from the electronic health record for each patient during the initial 6 hours after ICU admission with “baseline” corresponding to the initial values at ICU admission. Echocardiogram data was also collected, however this was not available for all patients. Vasopressor use was summarized hourly using the cumulative vasopressor index (CVI), which yields a numeric score that represents the dose and number of vasopressor agents used (19). CVI ≥2 represents a moderate vasopressor requirement and values > 4 represent high doses. Inodilators (milrinone and dobutamine) are not included in this index.
Shock. Author manuscript; available in PMC 2017 June 01.
Janiczek et al.
Page 4
Author Manuscript
Clinical outcomes were survival to hospital discharge and favorable neurologic outcome defined as a discharge cerebral performance category (CPC) 1 or 2. Both outcomes were binary. To assess the association between MAP and shock resolution, we used the surrogate lactate clearance (mmol/L/day) which in prior cardiac arrest studies has been associated with outcome. We extrapolated 24h clearance using the first two measures obtained in the ICU provided they were drawn at least two hours apart (four cases used first and third measures). Lactate values were a median of 6.5 hours apart (IQR 4.5 – 12 hours), the first value generally obtained within 1h of ICU admission.
Author Manuscript
We defined “early” resuscitation as the first 6h of ICU care. We calculated the mean of the initial 6h ICU MAP (MAP-6h) and CVI (CVI-6h) as well as the sum of fluid intake in the first 6h. To delineate resuscitation groups based on management differences, we created dichotomized groups of high vs. low fluid intake and CVI based on the median distributions in the entire cohort. This resulted in four resuscitation subgroups: 1.
Low fluids/low pressors: 6h fluid intake ≤700 ml, CVI700 ml, CVI700 ml, CVI≥1
Fluid intake=700 ml and average CVI=1 cutoffs approximated the cohort medians. Missing Data
Author Manuscript
Data was complete for all variables except the hourly heart rate (HR) and MAP. For MAP, we preferentially used invasive arterial MAP as recorded or by calculating the value from the arterial systolic and diastolic blood pressures using the equation MAP = [(systolic + 2* diastolic) / 3]. If this was missing or an arterial line was not placed, values were obtained from cuff measurements. If no hourly value was available for MAP or HR, we used the average value obtained from the hour before and after. We were missing 38/826 (4.6%) of HR and 56/826 (6.8%) of MAP values in 28/118 (24.7%) and 35/118 (29.7%) of subjects, respectively. HR and MAP missingness were correlated to one another (i.e., both data elements missing at same time; Spearman rho = 0.662, p < 0.001) but there was no association between missing data and shock severity (baseline MAP or CVI), injury severity (PCAC) or outcomes. Statistical Analyses
Author Manuscript
Analyses were performed with SPSS v.22 (IBM, Armonk, NY) by the team statistician (DW) independent of the investigators. R version 3.0.0 (R Foundation for Statistical Computing, Vienna, Austria) was used along with the user-written package “rms” to assess regression diagnostics and test the assumption of linear relationships via restricted cubic splines (20). Analyses involving lactate clearance were restricted to the subset with complete lactate clearance data (n=79). All other analyses were completed within the full cohort (n=118).
Shock. Author manuscript; available in PMC 2017 June 01.
Janiczek et al.
Page 5
Author Manuscript
Multivariable logistic regression tested the association of MAP-6h, IVF-6h, and CVI-6h with survival. We adjusted for all three of these variables simultaneously. Potential candidate covariates for the model included age, sex, OHCA, initial rhythm dichotomized as shockable (VF/VT) or not, PCAC (Pittsburgh Post-Cardiac Arrest Category) score, initial MAP and initial CVI dichotomized as not needing vasopressors (CVI=0; 78% of population) or needing vasopressors. In our model, we utilized PCAC, baseline MAP, and baseline vasopressor requirement, since these were felt to the most clinically significant. The PCAC is a validated injury severity score based on early neurologic exam and SOFA respiratory and cardiovascular subscales. PCAC 1 is a patient who is following commands (best prognosis) and PCAC 4 is a deeply comatose patient (worst prognosis)(19). The HosmerLemeshow test confirmed goodness-of-fit in adjusted logistic models. Similar multivariable regression could not be employed for good neurologic outcome due to limited good outcomes (n=21). In this multivariable model we therefore only included the most significant covariate (PCAC).
Author Manuscript
In a pre-specified analysis aimed at identifying a potential “optimal” resuscitation strategy, we compared clinical outcomes among the four resuscitation groups described above. We compared the proportion of patients surviving to hospital discharge across groups using the Fisher’s exact test. We used logistic regression to assess the association between resuscitation subgroup and clinical outcomes. The low fluid/low vasopressor subgroup was considered the reference group as it had the best outcomes and appeared to be the group with the lowest degree of shock. Due to the small sample size, further covariate adjustments could not be made.
Author Manuscript
We tested the correlation of MAP-6h, IVF-6h, and CVI-6h with lactate clearance as a surrogate for shock resolution. After using restricted cubic splines to confirm that the assumption of a linear relationship was not violated between these three variables and lactate clearance, we reported Pearson r correlations for these relationships. We compared mean lactate clearance by ANOVA using clinically relevant cut-points of < 65mmHg, 65-80 mmHg (10), and > 80 mmHg (11, 12). After using variance inflation factor (VIF) to rule out multicollinearity problems among MAP-6h, CVI-6h, and IVF-6h, we tested the association between these variables and lactate clearance by linear regression. We adjusted for these three variables simultaneously, as well as initial lactate, initial CVI, and initial MAP to account for shock severity. This model did not present major collinearity diagnostic issues (VIF or residuals), and the assumption of a linear relationship was confirmed to be acceptable through the use of restricted cubic splines in diagnostic testing
Author Manuscript
We compared ejection fraction between our 4 resuscitation groups using one-way ANOVA. Comparison of SpO2:FiO2 ratios over time was made using repeated measures ANOVA for the two intermediate subgroups (low fluids/high pressors and high fluids/low pressors).
Results 183 subjects were admitted to our ICUs within 2 hours of ROSC. 65 subjects died within the first 24 hours due to limitation of care or recurrent arrest without ROSC leaving 118 subjects in the final cohort (Fig. 1). A subset of the final cohort (n=79) had complete lactate
Shock. Author manuscript; available in PMC 2017 June 01.
Janiczek et al.
Page 6
Author Manuscript
clearance data available. Clinical features of the full cohort (n=118) are presented in Table 1. Compared to the full cohort, the lactate subset had more severe injury based on trends towards more vasopressor and inotrope use and worsened PCAC (21, 22) scores indicating more severe post-cardiac arrest illness. Clinical Outcomes 55/118 patients (46%) survived to hospital discharge and 21/118 (18%) had favorable neurologic outcome. Adjusting for shockable initial rhythm, OHCA, and PCAC score (p
Shock. Author manuscript; available in PMC 2017 June 01. Published in final edited form as: Shock. 2016 June ; 45(6): 613–619. doi:10.1097/SHK.0000000000000554.
HEMODYNAMIC RESUSCITATION CHARACTERISTICS ASSOCIATED WITH IMPROVED SURVIVAL AND SHOCK RESOLUTION AFTER CARDIAC ARREST
Author Manuscript
Jonathan A. Janiczek*, Daniel G. Winger†, Patrick Coppler‡,§, Alexa R. Sabedra*, Holt Murray§, Michael R. Pinsky§, Jon C. Rittenberger**, Joshua C. Reynolds††, and Cameron Dezfulian‡,§,‡‡ *School
of Medicine, University of Pittsburgh, Pittsburgh, PA
†Clinical ‡Safar
and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA
Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA
§Department
of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA
**Department
of Emergency Medicine, University of Pittsburgh, Pittsburgh, PA
††Department
of Emergency Medicine, Michigan State University College of Human Medicine, Grand Rapids, MI ‡‡Vascular
Medicine Institute, University of Pittsburgh, Pittsburgh, PA
Author Manuscript
Abstract Purpose—To determine which strategy of early post-cardiac arrest hemodynamic resuscitation was associated with best clinical outcomes. We hypothesized that higher mean arterial pressure (MAP) achieved using IV fluids over vasopressors would yield better outcomes.
Author Manuscript
Methods—Retrospective cohort study of post-cardiac arrest patients between March 2011 and June 2012. Patients successfully resuscitated from cardiac arrest, admitted to an ICU and surviving at least 24 hours were included. Patients missing data for >2 hours after ROSC were excluded. The institutional standard for post-resuscitation MAP was ≥65 mmHg with no guidelines on how MAP was supported. We examined the association between early (6h) average MAP, vasopressor use summarized as cumulative vasopressor index (CVI) and fluid intake with outcomes including survival to discharge, favorable neurologic outcome based on Cerebral Performance Category (CPC) 1 or 2, and the surrogate outcome measure of lactate clearance using Pearson correlation and multivariable regression.
Address Correspondence to: Cameron Dezfulian, MD, Safar Center for Resuscitation Research, 206B Hill Building, 3434 Fifth Avenue, Pittsburgh, PA 15215, P: (412) 383-3128, F: (412) 383-1080, [email protected]. Conflicts of Interest: Janiczek: No conflicts; Winger: No conflicts; Sabedra: No conflicts; Dezfulian: No conflicts; The remaining authors have no disclosures. This project was completed at the University of Pittsburgh Medical Center: Mercy Hospital
Janiczek et al.
Page 2
Author Manuscript
Results—Of 118 patients, 55 (46%) survived to hospital discharge, 21 (18%) with favorable neurologic outcome. Higher 6h mean CVI was independently associated with worsened survival (OR 0.67; 95% CI 0.53, 0.85; p = 0.001). Resuscitation subgroups receiving higher than median vasopressors had worsened survival to hospital discharge regardless of fluid intake. In addition, higher MAP-6h correlated with increased lactate clearance (r=0.29; p= 0.011) Conclusions—Early post-ROSC hemodynamic resuscitation achieving higher MAP using fluid preferentially over vasopressors is associated with improved survival to hospital discharge as well as better lactate clearance. Keywords Cardiac Arrest; Shock; Resuscitation; Post-Cardiac Arrest Syndrome; Hemodynamics; Vasopressors; Fluid Administration
Author Manuscript
Introduction
Author Manuscript
Shock, a component of the post-cardiac arrest syndrome, is prevalent after resuscitation from cardiac arrest (1). This state of hemodynamic compromise often persists after return of spontaneous circulation (ROSC), and is associated with both increased in-hospital mortality and diminished functional outcome (2). This post-ROSC shock state may be secondary to myocardial dysfunction (2-4), a sepsis-like state (5), or both. Prior reports have noted an association between vasopressor use and mortality (1, 6, 7), even though higher blood pressure is also associated with improved outcomes (6). While some post-ROSC patients preserve adequate mean arterial pressure (MAP) without any hemodynamic intervention, many require significant resuscitation to achieve an appropriate MAP. It is unknown whether volume resuscitation or vasopressor administration is preferable for the shock state postROSC.
Author Manuscript
After ROSC, hemodynamic dysfunction is the major extracerebral injury associated with inhospital mortality (1). Given the parallels between cardiac arrest and sepsis (cytokine storm and myocardial dysfunction)(5), the International Liaison Committee on Resuscitation (ILCOR) and American Heart Association (AHA) have adopted similar goal-directed hemodynamic treatment recommendations as those used for sepsis (8) but little direct evidence supports MAP targets or the optimal means to achieve MAP (9). Improved outcomes have been noted with MAP of 65-75 mmHg (10), 80-100 mmHg (11), and >100 mmHg (12) compared to historical controls with lower MAP. However, the ideal MAP after ROSC is unknown, and hemodynamic management is rarely explicitly defined in postresuscitation care observational studies (13). Optimization of cardiac output using fluids may improves tissue perfusion (14) over merely achieving MAP targets using vasopressors. This leaves considerable uncertainty surrounding the optimal post-cardiac arrest resuscitation strategy. To better define the various strategies for early post-ROSC resuscitation, we ascertained MAP, the volume of resuscitative fluid used, and the amount of vasopressor used for a cohort of post-cardiac arrest patients at our institution. We then tested the associations between resuscitation strategy and clinical outcomes, and in a subset examined the
Shock. Author manuscript; available in PMC 2017 June 01.
Janiczek et al.
Page 3
Author Manuscript
association with lactate clearance (7, 15-17). We hypothesized that achieving higher MAP using volume resuscitation preferentially to vasopressors would be associated with improved outcomes which may also manifest as faster lactate clearance.
Materials and Methods Data from all patients at UPMC Mercy Hospital who received chest compressions or defibrillation, either in the hospital or prior to arrival, are entered into a quality improvement (QI) registry. The University of Pittsburgh Institutional Review Board approved retrospective analysis of this data as exempt and waived the requirement for informed consent to permit acquisition of additional data to address our study hypotheses. Study Setting and Population
Author Manuscript Author Manuscript
Data are from a single university-affiliated hospital with 59 critical care beds staffed by a single intensivist group providing 24/7 coverage. During the study period the institutional target for post-resuscitation MAP was ≥65 mmHg. No protocol existed to assess volume status or to direct fluid intake vs. vasopressors to achieve goal MAP. Hypothermia (target temperature 33°C) was provided for 24h using intravascular cooling (Thermoguard XP, Zoll, Chelmsford, MA) to all comatose patients regardless of presenting rhythm. EEG use was at the discretion of the provider but is only available for episodic not continuous monitoring and from quality assurance data is generally used in ~50% of comatose patients at days 2-3. There are no institutional guidelines on neuroprognostication and this is left to the judgement of the critical care provider. Sedation is targeted in all critically ill patients to Riker 3-4 with occasional rare exceptions. Our ICUs employ daily sedation interruptions to minimize over-sedation. Recently we reported that for cardiac arrest patients admitted to this center during a time period inclusive of the study dates (18) the rate of survival to discharge was 41% and the rate of good neurologic outcome was 19%. Study Design This retrospective cohort study included all adult (age ≥18 years) patients successfully resuscitated from out of hospital cardiac arrest (OHCA) or in hospital cardiac arrest (IHCA) from March, 2011 to June, 2012 and admitted to the ICU. We excluded patients who did not survive 24 hours beyond hospital admission. Most of these excluded early deaths resulted from limitation of care (withdrawal of life support or limited resuscitation), which significantly impacted the aggressiveness of early resuscitation. Study Definitions and Outcome Measures
Author Manuscript
We collected vital signs, vasopressor and inotrope infusion rates, fluid intake, output and balance from the electronic health record for each patient during the initial 6 hours after ICU admission with “baseline” corresponding to the initial values at ICU admission. Echocardiogram data was also collected, however this was not available for all patients. Vasopressor use was summarized hourly using the cumulative vasopressor index (CVI), which yields a numeric score that represents the dose and number of vasopressor agents used (19). CVI ≥2 represents a moderate vasopressor requirement and values > 4 represent high doses. Inodilators (milrinone and dobutamine) are not included in this index.
Shock. Author manuscript; available in PMC 2017 June 01.
Janiczek et al.
Page 4
Author Manuscript
Clinical outcomes were survival to hospital discharge and favorable neurologic outcome defined as a discharge cerebral performance category (CPC) 1 or 2. Both outcomes were binary. To assess the association between MAP and shock resolution, we used the surrogate lactate clearance (mmol/L/day) which in prior cardiac arrest studies has been associated with outcome. We extrapolated 24h clearance using the first two measures obtained in the ICU provided they were drawn at least two hours apart (four cases used first and third measures). Lactate values were a median of 6.5 hours apart (IQR 4.5 – 12 hours), the first value generally obtained within 1h of ICU admission.
Author Manuscript
We defined “early” resuscitation as the first 6h of ICU care. We calculated the mean of the initial 6h ICU MAP (MAP-6h) and CVI (CVI-6h) as well as the sum of fluid intake in the first 6h. To delineate resuscitation groups based on management differences, we created dichotomized groups of high vs. low fluid intake and CVI based on the median distributions in the entire cohort. This resulted in four resuscitation subgroups: 1.
Low fluids/low pressors: 6h fluid intake ≤700 ml, CVI700 ml, CVI700 ml, CVI≥1
Fluid intake=700 ml and average CVI=1 cutoffs approximated the cohort medians. Missing Data
Author Manuscript
Data was complete for all variables except the hourly heart rate (HR) and MAP. For MAP, we preferentially used invasive arterial MAP as recorded or by calculating the value from the arterial systolic and diastolic blood pressures using the equation MAP = [(systolic + 2* diastolic) / 3]. If this was missing or an arterial line was not placed, values were obtained from cuff measurements. If no hourly value was available for MAP or HR, we used the average value obtained from the hour before and after. We were missing 38/826 (4.6%) of HR and 56/826 (6.8%) of MAP values in 28/118 (24.7%) and 35/118 (29.7%) of subjects, respectively. HR and MAP missingness were correlated to one another (i.e., both data elements missing at same time; Spearman rho = 0.662, p < 0.001) but there was no association between missing data and shock severity (baseline MAP or CVI), injury severity (PCAC) or outcomes. Statistical Analyses
Author Manuscript
Analyses were performed with SPSS v.22 (IBM, Armonk, NY) by the team statistician (DW) independent of the investigators. R version 3.0.0 (R Foundation for Statistical Computing, Vienna, Austria) was used along with the user-written package “rms” to assess regression diagnostics and test the assumption of linear relationships via restricted cubic splines (20). Analyses involving lactate clearance were restricted to the subset with complete lactate clearance data (n=79). All other analyses were completed within the full cohort (n=118).
Shock. Author manuscript; available in PMC 2017 June 01.
Janiczek et al.
Page 5
Author Manuscript
Multivariable logistic regression tested the association of MAP-6h, IVF-6h, and CVI-6h with survival. We adjusted for all three of these variables simultaneously. Potential candidate covariates for the model included age, sex, OHCA, initial rhythm dichotomized as shockable (VF/VT) or not, PCAC (Pittsburgh Post-Cardiac Arrest Category) score, initial MAP and initial CVI dichotomized as not needing vasopressors (CVI=0; 78% of population) or needing vasopressors. In our model, we utilized PCAC, baseline MAP, and baseline vasopressor requirement, since these were felt to the most clinically significant. The PCAC is a validated injury severity score based on early neurologic exam and SOFA respiratory and cardiovascular subscales. PCAC 1 is a patient who is following commands (best prognosis) and PCAC 4 is a deeply comatose patient (worst prognosis)(19). The HosmerLemeshow test confirmed goodness-of-fit in adjusted logistic models. Similar multivariable regression could not be employed for good neurologic outcome due to limited good outcomes (n=21). In this multivariable model we therefore only included the most significant covariate (PCAC).
Author Manuscript
In a pre-specified analysis aimed at identifying a potential “optimal” resuscitation strategy, we compared clinical outcomes among the four resuscitation groups described above. We compared the proportion of patients surviving to hospital discharge across groups using the Fisher’s exact test. We used logistic regression to assess the association between resuscitation subgroup and clinical outcomes. The low fluid/low vasopressor subgroup was considered the reference group as it had the best outcomes and appeared to be the group with the lowest degree of shock. Due to the small sample size, further covariate adjustments could not be made.
Author Manuscript
We tested the correlation of MAP-6h, IVF-6h, and CVI-6h with lactate clearance as a surrogate for shock resolution. After using restricted cubic splines to confirm that the assumption of a linear relationship was not violated between these three variables and lactate clearance, we reported Pearson r correlations for these relationships. We compared mean lactate clearance by ANOVA using clinically relevant cut-points of < 65mmHg, 65-80 mmHg (10), and > 80 mmHg (11, 12). After using variance inflation factor (VIF) to rule out multicollinearity problems among MAP-6h, CVI-6h, and IVF-6h, we tested the association between these variables and lactate clearance by linear regression. We adjusted for these three variables simultaneously, as well as initial lactate, initial CVI, and initial MAP to account for shock severity. This model did not present major collinearity diagnostic issues (VIF or residuals), and the assumption of a linear relationship was confirmed to be acceptable through the use of restricted cubic splines in diagnostic testing
Author Manuscript
We compared ejection fraction between our 4 resuscitation groups using one-way ANOVA. Comparison of SpO2:FiO2 ratios over time was made using repeated measures ANOVA for the two intermediate subgroups (low fluids/high pressors and high fluids/low pressors).
Results 183 subjects were admitted to our ICUs within 2 hours of ROSC. 65 subjects died within the first 24 hours due to limitation of care or recurrent arrest without ROSC leaving 118 subjects in the final cohort (Fig. 1). A subset of the final cohort (n=79) had complete lactate
Shock. Author manuscript; available in PMC 2017 June 01.
Janiczek et al.
Page 6
Author Manuscript
clearance data available. Clinical features of the full cohort (n=118) are presented in Table 1. Compared to the full cohort, the lactate subset had more severe injury based on trends towards more vasopressor and inotrope use and worsened PCAC (21, 22) scores indicating more severe post-cardiac arrest illness. Clinical Outcomes 55/118 patients (46%) survived to hospital discharge and 21/118 (18%) had favorable neurologic outcome. Adjusting for shockable initial rhythm, OHCA, and PCAC score (p
