A nurse in the emergency department is caring for a client who took 3 nitroglycerin tablets

We analyzed a total of 2594 patients, divided in 2 groups. A-first group contained 2246 patients and N-first group 348 patients, forming a time series of data. Patients were predominantly male 69.12%; vs 30.87% female. Average age was 63.72 years. Descriptive data are presented in Table 2.

Descriptive data on how different groups were formed are presented in Table 3. All figures presented were tested using Chi square of independence and Paired t test.

Giving the 1st dose of nitroglycerin a few minutes after aspirin resulted in a reduction of patients requiring a 3rd dose of nitroglycerin (Fig. 1a). The 1 dose nitroglycerin group has a linear upward trend line progression from A1 to A9 groups, with a slope of 1.35 (R2 0.66) and the 3 dose nitroglycerine group has downward slope of −1.26 (R2 0.75). This results in a 23.5% reduction of a 3rd nitroglycerin dose in the A9 group compared to the A1 group. Chi square of independence was found to be significant (×2 (16) =40.21, p = 0.00072). This finding has a linear progression from the A1 to the A9 group.

Nitroglycerin’s given A-first group

The same correlation was found when the 1 dose nitroglycerine group is compared to the sum of all additional nitroglycerin given (Fig. 1b). The analysis showed that there is a 24.3% reduction in dosing of any additional nitroglycerin after the first one in the A9 group with significant linear progression across all groups (R2 0.66). It is significant that in the A1 group there were 11.74% more patients who received additional nitroglycerin compared to the A9 group where 12.56% of patients received only 1 dose of nitroglycerin compared to all additional nitroglycerin. These data have significant chi square of independence (× 2 (8) =19.0, p = 0.0148).

This correlation was not found within the N1 group because the data were analyzed and were found statistically insignificant using chi square of independence.

The second set of analysis analyzed the subjective feeling of the patients after receiving each dose of medication. Similarly, as in the first set of analysis there is a linear trend from A1 to A9 groups. More patients were feeling “better” (+) than “same” (0) in groups where they received the first dose of nitroglycerin a few minutes after aspirin. Figure 2a shows the sum of 1 nitro and 2 nitro groups. The better (+) event has an up-sloping progression with a slope of 1.46 (R2 of 0.62) and the “same” or (0) event has a trend line slope of 0.6 (R2 0.25). This means that the trend lines are diverging and this results in 7.7% more (+) events than (0) in A9 group compared to (A1) group. Figure 2a was tested with a paired t-test because it is a set of paired data, derived from 1 and 2 nitroglycerine groups. There was a significant difference in the scores for “better” (+) (M = 160.56, SD = 62,52) and “same” (0) events (M = 111.56, SD = 35,74), conditions: t (8) =4,45, p = 0.0021.

Better (+) and Same (0) events a A-first group

Even though both 1 and 2 nitroglycerine groups independently had a similar linear progression and divergence they are presented together for simplicity sake. Same was done for 3rd and all the rest groups.

The 3rd and the rest of nitroglycerine subgroups had the opposite trend and the trend lines converge (Fig. 2b). This is shown in Fig. 2b where the “better” or (+) events have downward slope of − 1.37 (R2 0.66) and the “same” or (0) events have slope of − 0.72 (R2 0.27). This results in a change of negative 5.85% from A1 to A9, or more patients reported “same” than “better”. Data validity was also tested with paired t test with significant differences in the scores for “better” (+) (M = 91,67 SD = 60,8) and “same” (0) events (M = 64,67, SD = 35.79) conditions: t (8) =2.73, p = 0.0258.

This correlation was not found within the N1 group because the data were analyzed and were found insignificant using paired t-test.

Figure 3 presents the sum of all “better” (+) and “same” (0) events for A and N groups. There is a 39.6% difference between “better” and “same” events between A-group and N-group. Standalone statistical analysis of N-group was not possible because the data were not significant. However, even though statistical analysis of N-group was not significant it is a large number of patients (348). Because of this, the comparison of the sum of both groups has significance of its own showing the complete reverse status of these two groups.

Sum of (+) and (0) event between A-first and N-first group

In order to exclude that this trend of reduced nitroglycerin administration in later groups is due to increased use of pain medications we also tested administration of pain medications. We measured only pain medications given after the first nitroglycerin in order to better correlate between them. Patients received 3 types of pain medications:

• Morphine - 497 given

• Fentanyl - 302 given

• Midazolam - 7 given.

Descriptive data of this analysis are presented in Table 4.

Graphic presentation in opioids given is presented in Fig. 4. It is evident that the total number of patients that received opioids has a very weak downward slope of − 0.18 (with R2 0.036) from A1 to A9. However, we designed a coefficient of opioids to include the number of opioids given per group. The need to give opioids is directly proportional to the number of patients that received opioids and the number of opioids that they received and is inversely proportional by the number of patients that are in the group. This can mathematically be presented as coefficient:

Percentage of patients that received opioids in A-first group and coefficient of opioids

This coefficient of opioids regards the number of patients that received opioids and the number of opioids they received. This coefficient has a significant downward trend line with slope of 1.44 with a relatively significant R2 of 0.34. This shows that in later groups a smaller percentage of opioid “load” was needed. However, these data have an insignificant chi square of independence (× 2 (16) =18.1, p = 0.316). This means that giving opioids is not dependent on the previous nitroglycerine given or has any relationship between the groups. In other words, giving opioids did not influence the administration of nitroglycerin in the patients. (See supplementary 10).

N-first group had an insignificant number of opioids given and is not presented.

In order to find some reason why some patients received nitroglycerin soon after aspirin and some later (A1 through A9), or why some patients received nitroglycerin first we analyzed a number of vital signs and demographic data recorded in the NEMSIS dataset (See Supplementary 4, 5). We tested the averages of:

• Systolic blood pressure (SBP),

• Heart rate,

• Patient acuity at start and disposition

• Pulse oximetry findings,

• Pain severity on a scale from 1 to 10,

• Type of ischemia (STEMI or NON-STEMI),

• Age,

• Gender differences.

• Type of ECG changes

Descriptive data for these analyses are presented in Table 5.

No significant correlation was found for any of the vital signs, except for systolic blood pressure and age of the patients as presented on Figs. 5 and 6. Patient acuity test showed improved acuity at disposition for patients marked Red and Yellow but data were found statistically insignificant. See supplementary 16 and 17.

Systolic blood pressure in A-first group (mmHg)

Figure 5 shows a down sloping trend line with slope of 0.99 (R2 of 0.54) which shows that on average A9 group had 8.9 mmHg lower systolic blood pressure compared to A1 group, and this is a consistent trend from A1 to A9 group. To some patients, systolic blood pressure was measured several times and we only compared the average for the whole group. The rationale behind this decision was to find a pattern that can explain the postponing of nitroglycerin administration.

We found another significant trend in the A-first group regarding the average age. There is an up-sloping trend (slope 0.26 with R2 of 0.4) for the age of the patients from A1 to A9 group as presented in Fig. 6. This means older patients received nitroglycerin later in A-group.

No similar correlations and significant trends were found in N-group.

We analyzed which type of ECG changes were most prevalent within the cohort, and the result showed that than 92.71% were STEMI myocardial ischemia, and 7.28% were NON_STEMI as shown in Fig. 7. (See Supplementary 12, 13, 14) N-first group alone had similar ratio. Out of 348 patients in N-first group 323 cases or 92.81% were STEMI and 25 or 7.19% were NON-STEMI patient. (See supplementary 15).

Percent with STEMI vs NON-STEMI in all patients 9 both groups

Finding that more that 92.71% of all cohort-patients were with STEMI changes was surprising and we wanted to analyze if there are any changes in the findings in this subgroup. The same sets of analyses were conducted on the exclusive 2404 STEMI patients. Again only A-First group is presented, N-First group had insufficient data.

Figure 8a is very similar to Fig. 1a. The 1 dose nitroglycerin group has a linear upward trend line progression from A1 to A9 groups, with a slope of 1.53 (R2 0.63) and the 3 dose nitroglycerine group has downward slope of − 1.35 (R2 0.74). This results in a 25.9% (improvement of 2.4%) reduction of a 3rd nitroglycerin dose in the A9 group compared to the A1 group. Chi square of independence was found to be significant (× 2 (16) = 40.3, p = 0.00070).

Exclusive STEMI group – Nitroglycerin’s given in A-first group

The same correlation was found when the 1 dose nitroglycerine group is compared to the sum of all additional nitroglycerin given (Fig. 8b). The analysis showed that there is a 26.46% (improvement of 2.16%) reduction in dosing of any additional nitroglycerin after the first one in the A9 group with significant linear progression across all groups (R2 0.63 and 0.60). These data have significant chi square of independence (× 2 (8) = 19.2, p = 0.0133).

The second set of analysis shown in Fig. 9 is also very similar to Fig. 2. The better (+) event has an up-sloping progression with a slope of 1.64 (R2 of 0.62) and the “same” or (0) event has a trend line slope of 0.7 (R2 0.28). This means that the trend lines are diverging and this results in 8.46% (improvement of 0.76%) more (+) events than (0) in A9 group compared to A1 group. The paired t-test showed a significant difference in the scores for “better” (+) (M = 146.56, SD = 55,96) and “same” (0) events (M = 104.00, SD = 33,49), conditions: t (8) = 4,23, p = 0.0029.

Exclusive STEMI group – Better (+) and Same (0) events in a A-first group

The 3rd and all remaining nitroglycerine subgroups again had the opposite trend and the trend lines converge (Fig. 2b). This is shown in Fig. 2b where the “better” or (+) events have downward slope of − 1.29 (R2 0.65) and the “same” or (0) events have slope of − 0.79 (R2 0.35). This results in a change of negative 4.55% (reduced by 1.3%) from A1 to A9, or more patients reported “same” than “better”. Data validity was also tested with paired t test with significant differences in the scores for “better” (+) (M = 86,67 SD = 56,99) and “same” (0) events (M = 62,22, SD = 35.34) conditions: t (8) = 2.83, p = 0.0221.

Both test in the exclusive STEMI group of 2404 patients showed small improvements over the overall 2594 patients included in the study. The improvements are presented in Table 6.

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From: The timing of administering aspirin and nitroglycerin in patients with STEMI ECG changes alter patient outcome