Introduction
Congestive heart failure (CHF) affects approximately 5.7 million patients in the US, with one in nine death certificates mentioning heart failure.Reference Roger, Go and Lloyd-Jones1 Patients presenting with acute decompensated heart failure (ADHF) require urgent medical intervention to reduce the morbidity and mortality associated with rapid cardiopulmonary deterioration. Current treatment guidelines for ADHF include nitrates, morphine, diuretics, non-invasive ventilation and, when necessary, intubation and mechanical ventilation.Reference Jessup, Abraham and Casey2 Nitroglycerin is a systemic vasodilator that acts preferentially on the venous system to reduce cardiac preload. At higher doses it also acts on the arterial system, reducing afterload and improving cardiac output, making it an ideal treatment for patients in ADHF who tend to have high vascular resistance and hypertension.Reference Herling3
Administration of high-dose nitroglycerin is an effective treatment that has been shown to improve the respiratory symptoms associated with ADHF, and decrease the incidence of death due to myocardial infarction and mechanical ventilation, particularly when initiated early.Reference Cotter, Metzkor and Kaluski4-Reference Emerman6 Such doses are generally administered intravenously in the hospital setting, but the practical considerations of IV nitroglycerin storage and administration preclude the routine use of this medication in the prehospital setting.
A new protocol was recently developed by the New York State Western Regional Emergency Medical Advisory Council allowing paramedics to administer high-dose nitroglycerin for CHF using multiple sublingual tablets dosed according to patient blood pressure (Figure 1). Patients were treated with two sublingual tabs (0.8 mg) every five minutes when systolic blood pressure (SBP) was >160 mm Hg or three sublingual tabs (1.2 mg) every five minutes when SBP was >200 mm Hg.
Figure 1 Regional Protocol
One of the potential hazards of MSN administration in the field is hypotension following MSN administration. The current study is a retrospective analysis of prehospital data to determine the safety of the new protocol. Pre- and post-administration changes in systolic blood pressure were analyzed to address this issue.
Methods
Study Design
This study was a retrospective cohort study utilizing electronic prehospital patient care report (ePCR) data from a single large commercial provider.
Human Subject Review
This study was approved by the University at Buffalo Health Sciences Institutional Review Board.
Protocol and Study Population
Nitroglycerin 0.4 mg sublingual tabs (Nitro Stat, Parke-Davis, New York, New York USA) were utilized by New York State certified EMT-CCs (Emergency Medical Technicians-Critical Care) and paramedics during prehospital patient care. A computerized search for all documented prehospital nitroglycerin patients during the study period (January-June 2012) was performed. Case-patients were defined as those who received emergency medical services that resulted in at least one instance of MSN administration. The number of MSN administrations varied for each case-patient in the study. For each MSN administration, the timed set of vital signs immediately preceding and following (pre and post) was reviewed. The ePCR system documents time in one minute intervals. In instances where vital signs and medication administration had the same time stamp, it was assumed that the vitals were taken pre-MSN administration.
Analysis
MSN administrations were excluded from the analysis when pre or post vital signs were missing. Case-patients for whom no MSN administrations had complete pre and post vital signs data were eliminated. In case-patients who received multiple MSN administrations, each administration with complete vital signs was included in the analysis, but administrations with incomplete data were excluded. Data were entered into and analyzed in Microsoft Excel 2010 version 14.0 (Microsoft Corporation, Redmond, Washington USA).
Outcome
The primary endpoint was change in systolic blood pressure following each MSN administration. Blood pressure was measured in mm Hg. Hypotension was defined as systolic blood pressure (SBP) < 100. Administrations that resulted in hypotension were further reviewed.
Results
During the 6-month study period, there were 1,446 patients with any documented nitroglycerin administration, including basic life support (BLS) medication assists. One hundred patients had at least one instance of multiple simultaneous nitroglycerin administration by an advanced provider. Ninety-five MSN administrations in 75 case-patients had documented pre and post administration vital signs and were included in the analysis (Figure 2).
Figure 2 Inclusion Diagram
The average age of the case-patients was 65.7 (range 34-90) years. The patients were 54.7% male, 13.7% had documented chest pain, and 96.8% had documented shortness of breath.
Sixty-eight percent (65/95) of MSN administrations were of two tabs (Figure 3) administered simultaneously with a mean change in SBP of -16.4 mm Hg (SD = 31.9; range, +26 to -132). Thirty-one percent (29/95) of MSN administrations were of three tabs (Figure 4) administered simultaneously with a mean change in SBP of -10.1 mm Hg (SD = 28.1; range +59 to -79). A single MSN administration of four tabs occurred with a change in SBP of -31 mm Hg.
Figure 3 Pre/Post Systolic Blood Pressure for Administration of 2 Tabs Simultaneously
Figure 4 Pre/Post Systolic Blood Pressure for Administration of 3 Tabs Simultaneously
The average time between pre-administration vital signs and MSN administration was 4.2 minutes (SD = 3.7; range, 0-17). The average time between MSN administration and post administration vital signs was 4.6 minutes (SD = 2.7; range 1-12).
Systolic hypotension was documented in the post-administration vital signs of three patients (Table 1). The overall rate of post-MSN administration hypotension was 3.2% (3/95).
Table 1 Change in Systolic Blood Pressure by Number of Nitroglycerin Tablets Administered
The first case-patient was a 68-year-old Caucasian male with complaints of respiratory distress and chest pain. After treatment with two sublingual nitroglycerin tablets, his blood pressure decreased from 186/104 to 97/71. A follow-up blood pressure taken eight minutes later was 119/73. The patient remained stable and was transported to the hospital emergency department (ED) without incident.
The second case-patient was an 82-year-old Caucasian female being treated for shortness of breath and congestive heart failure. After treatment with two sublingual nitroglycerin tablets, her breathing improved but her blood pressure decreased from 185/91 to 66/47. Seven minutes later, a follow-up blood pressure was recorded at 100/56.
The third case-patient was a 71-year-old Caucasian female in severe respiratory distress. She was treated with two sublingual nitroglycerin tablets, after which her breathing slightly improved but her blood pressure decreased from 210/145 to 78/50. Seven minutes later, her blood pressure was recorded as 180/120. She remained stable and was transferred to the hospital ED without incident.
Based on documented pre-administration vital signs, adherence to the MSN administration protocol was inconsistent. Three case-patients were administered MSN following a documented SBP <160. None of these administrations resulted in hypotension.
Limitations
The study examined patients to whom MSN was administered. There were likely other patients treated during the study period for whom MSN was indicated but not administered. Similarly, more than one MSN administration may have been indicated for a patient based on the recommended five minute dosing, but only one MSN administration was administered.
The study was a retrospective review of prehospital data collected for clinical, non-research purposes. In the data set, vital signs were recorded separately from interventions and were not specifically linked to the administration of nitroglycerin. Vital signs also were not documented at fixed intervals, and other interventions may have taken place between pre and post vital signs. Other sets of vital signs that were obtained, but not documented, may have affected the care of the patients. This would explain some instances where the quantity of MSN administered seemed inconsistent with the protocol. Alternatively, other instances may represent protocol deviations.
This system of documentation may underestimate the frequency of hypotension by not capturing early hypotension that resolved prior to the documented set of vital signs or late hypotension that occurred after the last documented prehospital vital signs.
Discussion
Prompt recognition of ADHF symptoms and early initiation of appropriate therapy reduces morbidity and mortality and improves outcomes.Reference Emerman6, Reference Mebazaa, Gheorghiade and Pina7 However, the accurate diagnosis of ADHF and acute pulmonary edema (APE) may be challenging, particularly in the prehospital environment. Distinguishing between the respiratory distress symptoms of APE, chronic obstructive pulmonary disease (COPD) exacerbations, and pneumonia is often difficult or impossible on purely clinical grounds. Patients or bystanders may provide inadequate medical history or inaccurate history of present illness due to severe clinical symptoms. Even heart failure itself can be subdivided into several heart failure syndrome classifications, each with a distinct symptom profile and unique pathophysiology.Reference Mebazaa, Gheorghiade and Pina7 Treatment decisions in the setting of such diagnostic uncertainty may impose additional risks on a patient, yet must be made without delay to prevent further respiratory compromise.
Previous studies have examined the safety of different treatment algorithms in presumed ADHF in the prehospital setting.Reference Wuerz, Swope, Meador, Holliman and Roth8-Reference Bertini, Giglioli and Biggeri11 Mattu et al report that the use of standard-dose nitroglycerin by EMS personnel is not associated with adverse consequences, even if the diagnosis is incorrect.Reference Mattu and Lawner10 The current study addresses the safety of high-dose nitroglycerin administered as multiple sublingual tablets in an undifferentiated population of patients in respiratory distress. Although three case-patients (representing 3.2% of MSN administrations) developed hypotension following MSN administration, these episodes fully resolved and respiratory symptoms improved. This suggests that the protocol is a safe and potentially beneficial treatment option for prehospital patients in presumed ADHF and is unlikely to result in an adverse outcome if the etiology is other than heart failure.
Current guidelines for the treatment of decompensated heart failure include the use of non-invasive ventilation, diuretics, and morphine in addition to nitrates.Reference Jessup, Abraham and Casey2 The current study does not control for the effects of these additional treatments on patient outcome. It is possible that these therapies may have been responsible for the documented episodes of hypotension, or that the combination of nitroglycerin with other medications and/or non-invasive ventilation contributed to the overall change in the patients’ clinical and hemodynamic parameters, including those with improvement without hypotension. Furthermore, there is no available data on patient outcomes once they arrived in the emergency department, so it is possible that late episodes of hypotension caused by MSN have been missed.
The current study was designed to review the safety of a newly-established protocol for the treatment of ADHF. The study demonstrated a low incidence of hypotension, an important adverse event. Although long-term outcome data on the study population are not available, based on the infrequent development of hypotension, it is reasonable to conclude that the use of MSN is a safe and acceptable treatment alternative to high-dose IV nitroglycerin in the prehospital setting. Further investigation is also required to determine the effectiveness of initiating high-dose nitroglycerin prior to ED arrival relative to other available prehospital treatment options.
Conclusion
Hypotension was rare and self-limited in this retrospective cohort of prehospital patients receiving MSN for acute ADHF exacerbation with hypertension. Further study regarding the effectiveness of this prehospital intervention is needed.
Acknowledgement
The authors gratefully acknowledge the support of Robert Orlowski in data preparation and Joseph Consiglio in statistical analysis.
