Advanced cardiovascular life support guidelines exist, yet there are variations in clinical practice. Our study aims to describe the utilization of medications during resuscitation from in-hospital cardiopulmonary arrest. A retrospective review of patients who suffered a cardiopulmonary arrest from May 2008 to June 2014 was performed. Clinical and resuscitation data, including timing and dose of medications used, were extracted from the electronic medical record and comparisons made. A total of 94 patients were included in the study. Patients were divided into different groups based on the medication combination used during resuscitation: (1) epinephrine; (2) epinephrine and bicarbonate; (3) epinephrine, bicarbonate, and calcium; (4) epinephrine, bicarbonate, and epinephrine drip; and (5) epinephrine, bicarbonate, calcium, and epinephrine drip. No difference in baseline demographics or clinical data was present, apart from history of dementia and the use of calcium channel blockers. The number of medications given was correlated with resuscitation duration (Spearman’s rank correlation = 0.50, p <0.001). The proportion of patients who died during the arrest was 12.5% in those who received epinephrine alone, 30.0% in those who received only epinephrine and bicarbonate, and 46.7% to 57.9% in the remaining groups. Patients receiving only epinephrine had shorter resuscitation durations compared to that of the other groups (p <0.001) and improved survival (p = 0.003). In conclusion, providers frequently use nonguideline medications in resuscitation efforts for in-hospital cardiopulmonary arrests. Increased duration and mortality rates were found in those resuscitations compared with epinephrine alone, likely due to the longer resuscitation duration in the former groups.
Advanced cardiac life support is an unfortunate necessity in hospital systems. The fundamentals surrounding high quality resuscitation involve optimizing the favorable conditions in manually or mechanically induced circulation and ventilation. Although high quality remains the focus, there are unclear and limited data for promoting return of spontaneous circulation or improving survival with infusions such as epinephrine, bicarbonate, or calcium. Previous studies have shown varying utility with bicarbonate infusions in both in-hospital and out-of-hospital arrests. The use of calcium as a cardioprotective strategy has also been investigated. The most current 2015 guidelines caution against the use of routine bicarbonate or calcium infusions with the exception of very specific conditions. Although high-quality cardiopulmonary resuscitation is considered a necessity in all situations, with respect to pharmacologic intervention, there may be the temptation to “do more” than is recommended because the stakes are high. However, while tempting, the addition of additional therapies may have limited utility. The Mayo Registry for Telemetry Efficacy in Arrest (MR TEA) initiative was established to understand monitored events surrounding inpatient cardiopulmonary arrest. The goal of the current study is to describe the use of guideline directed pharmacological therapy during resuscitation efforts.
Methods
This retrospective cohort study was approved by the Institutional Review Board at Mayo Clinic. Using the MR TEA, 240 consecutive patients who experienced a cardiopulmonary arrest at Mayo Clinic in Jacksonville, Florida from May 2008 to June 2014 were identified. Only patients with a documented full code on admission were included. All patients in the study were on telemetry from the time of admission. If a patient experienced a subsequent cardiopulmonary arrest during the admission, only the first (index) event was included.
Members of the study team reviewed records to collect information on patient demographics and clinic characteristics, American College of Cardiology class indication for telemetry and Get With The Guidelines–based cardiopulmonary arrest data. Laboratory data were extracted from the day of admission and other clinical co-morbidities collected based on diagnoses and past medical histories as documented in the electronic medical record. Chronic kidney disease was defined by a glomerular filtration rate <60 mg/min/1.73m 2 and malignancy included all types, except nonmelanotic skin cancer. The primary clinical outcome for this study was code survival. Arrest survival information was obtained through MR TEA.
Administration of the following medications during the arrest was collected: epinephrine, vasopressin, amiodarone, bicarbonate, calcium, magnesium, lidocaine, and epinephrine drip. The first 3 medications were included in the 2015 guidelines. The remaining list of nonguideline medications was developed by the investigators based on current literature and clinical experience.
From the initial cohort of 240 patients, we grouped patients based on the types of medications given during the arrest. The following medication combinations with at least 10 patients were selected: (1) epinephrine; (2) epinephrine and bicarbonate; (3) epinephrine, bicarbonate, calcium, and epinephrine drip; (4) epinephrine, bicarbonate, and epinephrine drip; and (5) epinephrine, bicarbonate, and calcium drip. The final sample size was 94 patients. The different combinations of medications excluded from this study are presented in the Supplementary Table 1 .
Analyses for this exploratory study were primarily descriptive in nature with the sample median, minimum, and maximum reported for numeric data and number and percent reported for categorical variables. Comparisons of baseline information and arrest-related information between the 5 groups were performed using the Fisher’s exact tests for categorical variables and Kruskal–Wallis tests for numeric variables for the purpose of identifying potentially confounding variables. Correlations of arrest duration with number of medications and number of doses were explored using the Spearman’s rank correlation test. For the primary analysis, comparison of code survival between the 5 medication groups was explored using the Fisher’s exact tests. p Values of 0.05 or less were considered statistically significant without adjustment for multiple testing. Statistical analyses were performed using SAS, version 9.4 (SAS Institute Inc., Cary, North Carolina).
Results
Among the 94 patients included in this study, 50 (53%) were male and the median age was 65 years (range, 28 to 93 years). Clinical data and arrest-related information are summarized separately for the 5 medication groups in Tables 1 and 2 . Potentially confounding variables included dementia (p = 0.036), calcium channel blocker use before admission (p = 0.028), first pulseless rhythm (p = 0.031), and arrest duration (p <0.001). Most patients in all groups were defined as American College of Cardiology class 1 indication for telemetry. No statistical difference in the presence of a shockable rhythm, defibrillation attempt, or time from arrest to resuscitation was seen. In an exploratory analysis, there was evidence of a correlation between resuscitation duration and the number of doses of medication given (Spearman’s rank correlation = 0.60, p <0.001) in addition to the number of different medications administered (Spearman’s rank correlation = 0.50, p <0.001). Among the 70 patients who were administered at least one nonguideline medication, only 4 (6%) were administered the first nonguideline medication before epinephrine. Medication dose information is summarized in Table 3 .
| Characteristic | Epinephrine (N=24) | Epinephrine & Bicarbonate (N=20) | Epinephrine, Bicarbonate, Calcium, & Epinephrine Drip (N=19) | Epinephrine, Bicarbonate, & Epinephrine Drip (N=16) | Epinephrine, Bicarbonate, & Calcium (N=15) | P value |
|---|---|---|---|---|---|---|
| Male sex | 11 (46%) | 12 (60%) | 11 (58%) | 7 (44%) | 9 (60%) | 0.77 |
| Age (years) | 67 (28-93) | 68 (34-90) | 66 (28-88) | 63 (35-88) | 61 (30-91) | 0.94 |
| White | 18 (75%) | 16 (80%) | 15 (79%) | 12 (75%) | 11 (73%) | 0.99 |
| Myocardial infarction | 4 (17%) | 2 (10%) | 4 (21%) | 1 (6%) | 2 (13%) | 0.77 |
| Coronary artery disease | 9 (38%) | 6 (30%) | 5 (26%) | 2 (13%) | 4 (27%) | 0.55 |
| Atrial fibrillation/flutter | 8 (33%) | 5 (25%) | 6 (32%) | 4 (25%) | 3 (20%) | 0.91 |
| Dementia | 0 (0%) | 0 (0%) | 0 (0%) | 1 (6%) | 2 (13%) | 0.036 |
| Pacemaker or ICD | 2 (8%) | 3 (15%) | 2 (11%) | 2 (13%) | 1 (7%) | 0.96 |
| Hypertension | 15 (63%) | 13 (65%) | 14 (74%) | 12 (75%) | 7 (47%) | 0.49 |
| COPD/asthma | 2 (8%) | 6 (30%) | 4 (21%) | 2 (13%) | 5 (33%) | 0.23 |
| Diabetes mellitus | 7 (29%) | 6 (30%) | 9 (47%) | 5 (31%) | 6 (40%) | 0.73 |
| Current smoker | 3 (13%) | 2 (10%) | 2 (11%) | 1 (6%) | 2 (13%) | 0.97 |
| Malignancy (excluding skin cancer) | 8 (33%) | 5 (25%) | 5 (26%) | 3 (19%) | 4 (27%) | 0.90 |
| Chronic kidney disease | 7 (29%) | 10 (50%) | 4 (21%) | 6 (38%) | 8 (53%) | 0.22 |
| Beta blocker | 6 (25%) | 8 (40%) | 9 (47%) | 8 (50%) | 5 (33%) | 0.47 |
| Calcium channel blocker | 4 (17%) | 5 (25%) | 0 (0%) | 4 (25%) | 0 (0%) | 0.028 |
| Anti-arrhythmic medication | 4 (17%) | 3 (15%) | 1 (5%) | 2 (13%) | 2 (13%) | 0.86 |
| ACC Class indication for telemetry | 0.61 | |||||
| 1 | 15 (79%) | 11 (65%) | 11 (65%) | 12 (75%) | 12 (92%) | |
| 2 | 3 (16%) | 4 (24%) | 5 (29%) | 3 (19%) | 0 (0%) | |
| 3 | 1 (5%) | 2 (12%) | 1 (6%) | 1 (6%) | 1 (8%) | |
| Hemoglobin (g/dL) | 10.5 (7.1-15.3) | 12.3 (6.4-15.8) | 10.7 (8.7-15.9) | 11.5 (6.8-17.2) | 13.1 (7.5-16.8) | 0.43 |
| Creatinine (g/dL) | 1.25 (0.6-8.3) | 1.4 (0.6-6.5) | 1.2 (0.5-4.0) | 1.2 (0.4-5.1) | 1.4 (0.5-8.3) | 0.81 |
| Potassium (mmol/L) | 4.2 (3.2-6.8) | 4.2 (3.1-6.1) | 4.1 (3.4-6.1) | 4.1 (2.9-6.4) | 3.9 (3-5.1) | 0.19 |
| Body mass index (kg/m 2 ) | 27.6 (17.0-37.0) | 26.2 (19.0-40.2) | 27.1 (17.5-48.0) | 27.5 (14.7-38.1) | 28.7 (18.7-40.3) | 0.88 |
| Systolic blood pressure (mm Hg) | 124 (79-187) | 123 (73-163) | 116 (50-163) | 118 (76-154) | 121 (85-162) | 0.69 |
| Diastolic blood pressure (mm Hg) | 71 (29-107) | 69 (39-112) | 65 (27-83) | 80 (34-112) | 64 (50-91) | 0.20 |
| Heart rate (beats per min) | 99 (58-134) | 79 (53-129) | 84 (63-127) | 86 (59-145) | 90 (47-156) | 0.38 |
| Ejection fraction (%) | 60 (25-71) | 61 (10-75) | 55 (10-73) | 59 (15-80) | 61 (35-81) | 0.98 |
| Illness category | 0.10 | |||||
| Medical cardiac | 9 (38%) | 1 (5%) | 7 (37%) | 6 (38%) | 3 (20%) | |
| Medical non-cardiac | 12 (50%) | 14 (70%) | 11 (58%) | 8 (50%) | 10 (67%) | |
| Surgical cardiac | 0 (0%) | 1 (5%) | 0 (0%) | 2 (13%) | 1 (7%) | |
| Surgical non-cardiac | 3 (13%) | 4 (20%) | 1 (5%) | 0 (0%) | 1 (7%) |
| Characteristic | Epinephrine (N=24) | Epinephrine & Bicarbonate (N=20) | Epinephrine, Bicarbonate, Calcium, & Epinephrine Drip (N=19) | Epinephrine, Bicarbonate, & Epinephrine Drip (N=16) | Epinephrine, Bicarbonate, & Calcium (N=15) | P value |
|---|---|---|---|---|---|---|
| Coded in ICU | 13 (54%) | 13 (65%) | 13 (68%) | 12 (75%) | 9 (60%) | 0.73 |
| Immediate cause of arrest | 0.080 | |||||
| Hypotension | 14 (64%) | 9 (45%) | 10 (53%) | 8 (53%) | 7 (50%) | |
| Respiratory distress | 4 (18%) | 8 (40%) | 4 (21%) | 4 (27%) | 0 (0%) | |
| Ventricular tachycardia/fibrillation | 0 (0%) | 0 (0%) | 0 (0%) | 1 (7%) | 0 (0%) | |
| Asystole | 0 (0%) | 0 (0%) | 1 (5%) | 0 (0%) | 1 (7%) | |
| Bradycardia | 0 (0%) | 1 (5%) | 2 (11%) | 0 (0%) | 1 (7%) | |
| Pulseless electrical activity | 2 (9%) | 0 (0%) | 1 (5%) | 1 (7%) | 0 (0%) | |
| Arrhythmia | 2 (9%) | 0 (0%) | 0 (0%) | 0 (0%) | 2 (14%) | |
| Metabolic | 0 (0%) | 2 (10%) | 0 (0%) | 1 (7%) | 1 (7%) | |
| Other | 0 (0%) | 0 (0%) | 1 (5%) | 0 (0%) | 2 (14%) | |
| First pulseless rhythm | 0.031 | |||||
| Pulseless electrical activity | 12 (52%) | 8 (40%) | 14 (74%) | 10 (63%) | 2 (13%) | |
| Asystole | 6 (26%) | 9 (45%) | 2 (11%) | 5 (31%) | 9 (60%) | |
| Ventricular fibrillation/tachycardia | 2 (9%) | 1 (5%) | 1 (5%) | 1 (6%) | 3 (20%) | |
| Bradycardia | 3 (13%) | 2 (10%) | 2 (11%) | 0 (0%) | 1 (7%) | |
| Shockable rhythm | 2 (8%) | 1 (5%) | 1 (5%) | 1 (6%) | 3 (20%) | 0.64 |
| Defibrillation during resuscitation effort | 2 (8%) | 1 (5%) | 2 (11%) | 2 (13%) | 4 (27%) | 0.43 |
| Hypothermia protocol following resuscitation | 3 (13%) | 1 (5%) | 1 (5%) | 1 (6%) | 1 (7%) | 0.92 |
| Cardiac interventions used following resuscitaton | 1 (4%) | 0 (0%) | 1 (5%) | 1 (6%) | 0 (0%) | 0.87 |
| Time from arrest to CPR (min) | 0 (0-3) | 0 (0-4) | 0 (0-7) | 0 (0-2) | 0 (0-0) | 0.58 |
| Duration of arrest (min) | 11 (4-25) | 17 (5-60) | 28 (8-77) | 23 (8-49) | 17 (6-45) | <0.001 |
| Medication dose information | Epinephrine (N=24) | Epinephrine & Bicarbonate (N=20) | Epinephrine, Bicarbonate, Calcium, & Epinephrine Drip (N=19) | Epinephrine, Bicarbonate, & Epinephrine Drip (N=16) | Epinephrine, Bicarbonate, & Calcium (N=15) |
|---|---|---|---|---|---|
| Epinephrine (number of doses) | |||||
| 1 | 15 (63%) | 11 (55%) | 3 (16%) | 5 (31%) | 3 (20%) |
| 2 | 8 (33%) | 2 (10%) | 3 (16%) | 2 (13%) | 3 (20%) |
| 3 | 1 (4%) | 2 (10%) | 3 (16%) | 3 (19%) | 1 (7%) |
| 4 | 0 (0%) | 3 (15%) | 2 (11%) | 2 (13%) | 6 (40%) |
| 5 or more | 0 (0%) | 2 (10%) | 8 (42%) | 4 (25%) | 2 (13%) |
| Epinephrine (total dose [mg]) | 1.0 (0.5-2.0) | 1.3 (1.0-5.0) | 4.0 (1.0-5.0) | 2.3 (1.0-14.0) | 4.0 (1.0-6.0) |
| Epinephrine (number of minutes to initial dose) | 1 (0-18) | 1 (0-7) | 1 (0-6) | 1 (0-5) | 1 (1-5) |
| 0-3 | 18 (75%) | 15 (75%) | 18 (95%) | 14 (88%) | 12 (80%) |
| 4-6 | 3 (13%) | 4 (20%) | 1 (5%) | 2 (13%) | 3 (20%) |
| 7-9 | 1 (4%) | 1 (5%) | 0 | 0 | 0 |
| 10-12 | 1 (4%) | 0 | 0 | 0 | 0 |
| >12 | 1 (4%) | 0 | 0 | 0 | 0 |
| Bicarbonate (number of doses) | N/A | ||||
| 1 | 12 (60%) | 7 (37%) | 8 (50%) | 9 (60%) | |
| 2 | 7 (35%) | 4 (21%) | 6 (38%) | 4 (27%) | |
| 3 | 1 (5%) | 3 (16%) | 1 (6%) | 1 (7%) | |
| 4 | 0 | 3 (16%) | 0 | 1 (7%) | |
| ≥5 | 0 | 2 (11%) | 1 (6%) | 0 | |
| Bicarbonate (total dose [ampule]) | N/A | 2.0 (1.0-4.0) | 3 (1.0-6.0) | 2.0 (0.5-5.0) | 2.0 (1.0-7.0) |
| Bicarbonate (number of minutes to initial dose) | N/A | 4 (0-40) | 6 (0-24) | 7 (0-45) | 4 (1-19) |
| 0-3 | 9 (45%) | 8 (42%) | 5 (31%) | 5 (33%) | |
| 4-6 | 6 (30%) | 2 (11%) | 3 (19%) | 3 (20%) | |
| 7-9 | 1 (5%) | 6 (32%) | 2 (13%) | 4 (27%) | |
| 10-12 | 2 (10%) | 0 | 2 (13%) | 1 (7%) | |
| >12 | 2 (10%) | 3 (16%) | 4 (25%) | 2 (13%) | |
| Calcium (number of doses) | N/A | N/A | N/A | ||
| 1 | 15 (79%) | 12 (80%) | |||
| 2 | 4 (21%) | 3 (20%) | |||
| Calcium (total dose [g]) | N/A | N/A | 1.0 (1.0-4.0) | N/A | 1.0 (1.0-6.0) |
| Calcium (number of minutes to initial dose) | N/A | N/A | 7 (1-52) | N/A | 6 (1-24) |
| 0-3 | 4 (21%) | 4 (27%) | |||
| 4-6 | 4 (21%) | 4 (27%) | |||
| 7-9 | 3 (16%) | 1 (7%) | |||
| 10-12 | 3 (16%) | 4 (27%) | |||
| >12 | 5 (26%) | 2 (13%) | |||
| Epinephrine drip (initial rate [mcg/min]) | N/A | N/A | 2.0 (0.1-100.0) | 5.5 (0.4-100.0) | N/A |
| Epinephrine drip (number of minutes to initial dose) | N/A | N/A | 10 (0-56) | 11 (3-45) | N/A |
| 0-3 | 3 (16%) | 1 (6%) | |||
| 4-6 | 2 (11%) | 5 (31%) | |||
| 7-9 | 3 (16%) | 1 (6%) | |||
| 10-12 | 3 (16%) | 2 (13%) | |||
| >12 | 8 (42%) | 7 (44%) | |||
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