Sublingual nitroglycerin for early blood pressure control in hypertensive emergencies: observations from an emergency department clinical audit in Sri Lanka

Sublingual nitroglycerin for early blood pressure control in hypertensive emergencies:... Objective: Hypertensive emergencies are potentially life threatening and require prompt blood pressure control with intravenous agents. Preparation of intravenous infusions is time consuming. Usefulness of sublingual nitroglyc- erin in this setting is not known. We aimed to assess the benefit of sublingual nitroglycerin as a bridge to IV therapy. In a clinical audit in an emergency department, patients presenting with hypertensive emergencies requiring intrave- nous nitroglycerin were administered single spray of sublingual nitroglycerin awaiting commencement of intrave- nous infusion. Blood pressure was monitored every 5 min to observe the degree and speed of reduction. Results: Thirty-seven patients met the selection criteria. Mean age was 65.8 years (SD 7.04), and 29 were males (88.4%). Mean values of systolic, diastolic and mean blood pressures on admission were 217, 137, 163 mmHg. At 5 and 10 min after sublingual nitroglycerin, mean reduction of mean arterial blood pressure by 12.3 and 16.3% was achieved. Only 2 patients (5.4%) showed an overcorrection of blood pressure. Minimum of 15 min were required to set up a nitroglycerin intravenous infusion. Sublingual nitroglycerin spray allows rapid blood pressure control in hypertensive emergencies and is a useful bridge during the time to prepare intravenous infusion. Keywords: Hypertensive emergency, Sublingual nitroglycerin, Blood pressure control syndrome due to its favourable effect in reducing preload Introduction and cardiac output [3]. It is useful as second line agent Hypertensive emergency is an acute elevation of blood in hypertensive emergencies due to acute sympathetic pressure (180/120 mmHg) associated with end organ crisis (as in cocaine, amphetamines, monoamine oxidase damage [1]. In Sri Lanka, hypertensive diseases were the inhibitor toxicities, Irukandji Syndrome) [3]. The recom twelfth leading cause for in-hospital deaths during 2015 - (3.4 deaths per 100,000 population) while deaths due mended mean arterial pressure (MAP) reduction in these to Ischemic Heart Diseases are the leading cause (29.7 conditions is up to 25% for the first 24 h, and over-reduc - deaths per 100,000) [2]. tion might cause end organ ischemia and more harm [3]. Nitroglycerin is a potent venodilator, showing arterial Sublingual nitroglycerin is widely used for its antian- dilation only at very high doses. The use of sublingual, ginal properties. It is unlikely to be useful for definitive topical or IV nitroglycerin infusion is recommended management of hypertensive emergencies or urgencies as a first line agent in blood pressure control in acute due to short duration of action and variable absorption. hypertensive pulmonary oedema and in acute coronary However, its convenient use, ease of administration and rapid onset of action make it an ideal agent for rapid blood pressure control until definitive therapy is com - *Correspondence: dissanayakeha@gmail.com menced in the emergency department or in pre-hospital University Medical Unit, National Hospital of Sri Lanka, Colombo, Sri Lanka setting. There are no studies describing this utility of Full list of author information is available at the end of the article © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/ publi cdoma in/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Prasanna et al. BMC Res Notes (2018) 11:355 Page 2 of 3 sublingual nitroglycerin. We analysed data from a clini- Table 1 Clinical presentations of  hypertensive emergencies (N = 37) cal audit to assess the effectiveness of sublingual nitro - glycerin spray, as a bridging option during the inevitable Presentation Number Percentage (%) delay in setting up IV nitroglycerin. of patients Pulmonary oedema 16 43.2 Main text Acute coronary syndrome 7 18.9 Methods Neurological symptoms/signs 14 37.9 Design and setting (excluding stroke) A clinical audit was conducted at the emergency depart- ment of a tertiary care centre in Sri Lanka from August, 2017 to December, 2017. Patients presenting with hyper- Table 2 shows the blood pressure on admission and the tensive emergencies who required intravenous nitro- reductions in blood pressure 5 and 10  min after sublin- glycerin administration were selected by convenient gual nitroglycerin. Rapid blood pressure reduction was sampling. achieved with single puff of sublingual nitroglycerin spray. Only one patient had over-reduction of MAP more Selection of participants than 25% at 5  min (28%), which improved to 22% at Inclusion criteria were severe hypertension (defined as 10 min, while another patient who had 18% reduction at systolic blood pressure 180 mmHg or more and/or dias- 5 min had further reduced MAP by 29.5% at 10 min. tolic blood pressure 120  mmHg or more) with evidence Minimum delay from decision to commence IV nitro- of end organ dysfunction. Presence of clinical features glycerin to commencement of therapy was 15 min (mean of heart failure (dyspnoea, orthopnoea, bibasal crackles, 27  min) and was due to delays in gaining IV access and hypoxia SpO2 < 94% in the absence of chronic lung dis- preparation and setting up of the solution for infusion. ease), or angina with electrocardiographic changes sug- gestive of ischemia or neurological symptoms and/or Discussion signs (severe headache, visual blurring, altered conscious Rapid and controlled reduction of blood pressure is the level, papilloedema) were considered as evidence for end main aim in management of hypertensive emergencies. organ dysfunction. Suspected or confirmed aortic dissec - Intravenous administration of antihypertensives are tion, intracranial haemorrhage or stroke were excluded required. However, setting up an intravenous infusion from the study as their blood pressure goals and phar- consumes time, during which patient remains sympto- macological preferences are different. All participants matic and may even deteriorate. We observed that mean or next of kin (where patients’ capacity was limited due time taken for commencement of IV infusion from the to the acute illness) provided informed consent prior to time of deciding to treat is 27 min. Fastest time achieved selection. was 15 min. Therefore it is important to have an alternative strategy Observations which can be rapidly administered and could produce Upon diagnosis of hypertensive emergency that require rapid effect. It is not critical for it to be highly efficacious IV nitroglycerin infusion, patients were administered or long lasting as its role is to bridge the time until defini - single puff of nitroglycerin spray sublingually (0.4  mg). tive IV preparation is ready to use. Nitroglycerin sublin- Blood pressure was monitored every 5 min by automated gual spray has the advantages of being easy to administer monitoring machines using arm blood pressure cuff and (without a need for IV access) and having rapid absorp- was confirmed with manual blood pressure measurement tion and onset of action. Therapeutic utility of nitroglyc - with a mercury sphygmomanometer and systolic, dias- erin has been questioned at times due to its venodilatory tolic and mean arterial blood pressures (SBP, DBP and effects, potential to reduce cardiac output and cause MAP respectively) were recorded. Time taken to prepare reflex tachycardia [4]. However one recent study demon - the IV nitroglycerin infusion was noted. Other regular strated effective blood pressure reduction with sublingual medical management was continued unchanged accord- nitroglycerin in hypertensive urgencies [5]. Yet it is not ing to unit protocols. known whether sublingual nitroglycerin could achieve clinically relevant blood pressure reduction for a brief Results duration in a hypertensive emergency. Our analysis was Thirty seven patients met the selection criteria for aimed to answer this question. enrolment. Mean age was 65.6  years and 29 were males Findings of this clinical audit demonstrate that sub- (88.4%). Their clinical presentations are summarized in lingual nitroglycerin is efficacious, rapid in onset and Table 1. Prasanna et al. BMC Res Notes (2018) 11:355 Page 3 of 3 Table 2 Blood pressure on admission and after treatment with sublingual nitroglycerin On admission 5 min after spray 10 min after spray Mean Reduction from baseline Mean Reduction (%) from baseline (%) Systolic BP 217.0 (14.7) 197.8 (13.3) 8.7 188.5 (9.6) 13.1 Diastolic BP 136.2 (9.6) 115.5 (12.6) 15.1 110.3 (9.9) 19.0 Mean BP 163.2 (8.1) 143.0 (9.9) 12.3 136.4 (7.8) 16.3 Blood pressure values are mean (SD). BP blood pressure Author details achieved desired blood pressure control. This is in keep - Emergency Medicine, Post Graduate Institute of Medicine, University ing with its known pharmacokinetic properties, being of Colombo, Colombo, Sri Lanka. University Medical Unit, National Hospital rapidly absorbed through mucous membrane of oral cav- of Sri Lanka, Colombo, Sri Lanka. Department of Clinical Medicine, University of Colombo, Colombo, Sri Lanka. ity. Only one patient experience sustained over correc- tion of blood pressure, exceeding 25% reduction of MAP. Acknowledgements These findings have two important implications. Firstly, We thank the staff of the emergency department for their assistance and all the patients and family who participated in the audit. we suggest that sublingual nitroglycerin spray can be a useful adjunct in the management of a hypertensive Competing interests emergency until parental preparation is prepared, thus The authors declare that they have no competing interests. preventing complications due to unavoidable delays. Sec- Availability of data and materials ondly, this also indicates the potential usefulness of sub- Patient data from the audit are available with the GRC for reference if required. lingual nitroglycerin spray in out-of-hospital setting for Consent for publication paramedical services in better management of hyperten- Not applicable. sive emergencies. Therefore we conclude that sublingual nitroglycerin Ethics approval and consent to participate Data were obtained from a clinical audit and ethical approval was waived by spray is effective in reducing blood pressure in a hyper - the Ethics Review Committee of Asiri Surgical Hosptal according to Health Care tensive emergency, until IV preparation is made available. Quality Improvement Partnership Guide to managing ethical issues in quality We suggest that potential use of sublingual nitroglycerin improvement or clinical audit projects (February 2017). Patients/next of kin provided written informed consent to be included in the audit. in hypertensive emergencies should be studied further, in a larger population, with a control group with prospec- Funding tive follow up to determine final outcome. None. Publisher’s Note Limitations Springer Nature remains neutral with regard to jurisdictional claims in published There are few limitations in our study. Firstly, it is lim - maps and institutional affiliations. ited by small sample size. Secondly, effect of nitroglycerin Received: 10 February 2018 Accepted: 31 May 2018 was not compared against a control or a placebo. Thirdly, effect of early correction of high blood pressure on mor - tality, duration of hospital stay, need for other antihyper- tensives or morbidity were not assessed. Fourthly we did References not observe any adverse effects of therapy probably due 1. Chobanian AV, Bakris GL, Black HR, et al. Joint National Committee on to the good safety profile of this medication and also due Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure to the small sample size that was not adequate to deter- Education Program Coordinating Committee. Seventh Report of the Joint mine more rare adverse events. National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206. 2. Annual Health Bulletein. Ministry of Health. Nutrition and Indigenous Medicine, Abbreviations Sri Lanka. 2015. p. 33–38. http://www.healt h.gov.lk/moh_final /engli sh/publi c/ BP: blood pressure; DBP: diastolic blood pressure; IV: intravenous; MAP: mean elfin der/files /publi catio ns/AHB/2017/AHB%20201 5.pdf . Accessed 2 Jan 2018. arterial pressure; SBP: systolic blood pressure. 3. Tintinalli J, Stapczynski J, Ma O, Yealy D, Meckler G, Cline D. Tintinalli’s emer- gency medicine. New York: McGraw-Hill Education; 2016. p. 399–405. Authors’ contributions 4. Varon J, Marik PE. Clinical review: the management of hypertensive crisis. GRC conceived the concept and research question, designed and conducted Crit Care. 2003;7(5):374–84. https ://doi.org/10.1186/cc235 1. the audit. NP reviewed literature and collected data. NP and HAD analysed 5. Maleki A, Sadeghi M, Zaman M, Tarrahi MJ, Nabatchi B. Nifedipine, cap- data and prepared the manuscript. All authors read and approved the final topril or sublingual nitroglycerin, which can reduce blood pressure the manuscript. most? ARYA Atheroscler. 2011;7(3):102–5. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png BMC Research Notes Springer Journals

Sublingual nitroglycerin for early blood pressure control in hypertensive emergencies: observations from an emergency department clinical audit in Sri Lanka

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Abstract

Objective: Hypertensive emergencies are potentially life threatening and require prompt blood pressure control with intravenous agents. Preparation of intravenous infusions is time consuming. Usefulness of sublingual nitroglyc- erin in this setting is not known. We aimed to assess the benefit of sublingual nitroglycerin as a bridge to IV therapy. In a clinical audit in an emergency department, patients presenting with hypertensive emergencies requiring intrave- nous nitroglycerin were administered single spray of sublingual nitroglycerin awaiting commencement of intrave- nous infusion. Blood pressure was monitored every 5 min to observe the degree and speed of reduction. Results: Thirty-seven patients met the selection criteria. Mean age was 65.8 years (SD 7.04), and 29 were males (88.4%). Mean values of systolic, diastolic and mean blood pressures on admission were 217, 137, 163 mmHg. At 5 and 10 min after sublingual nitroglycerin, mean reduction of mean arterial blood pressure by 12.3 and 16.3% was achieved. Only 2 patients (5.4%) showed an overcorrection of blood pressure. Minimum of 15 min were required to set up a nitroglycerin intravenous infusion. Sublingual nitroglycerin spray allows rapid blood pressure control in hypertensive emergencies and is a useful bridge during the time to prepare intravenous infusion. Keywords: Hypertensive emergency, Sublingual nitroglycerin, Blood pressure control syndrome due to its favourable effect in reducing preload Introduction and cardiac output [3]. It is useful as second line agent Hypertensive emergency is an acute elevation of blood in hypertensive emergencies due to acute sympathetic pressure (180/120 mmHg) associated with end organ crisis (as in cocaine, amphetamines, monoamine oxidase damage [1]. In Sri Lanka, hypertensive diseases were the inhibitor toxicities, Irukandji Syndrome) [3]. The recom twelfth leading cause for in-hospital deaths during 2015 - (3.4 deaths per 100,000 population) while deaths due mended mean arterial pressure (MAP) reduction in these to Ischemic Heart Diseases are the leading cause (29.7 conditions is up to 25% for the first 24 h, and over-reduc - deaths per 100,000) [2]. tion might cause end organ ischemia and more harm [3]. Nitroglycerin is a potent venodilator, showing arterial Sublingual nitroglycerin is widely used for its antian- dilation only at very high doses. The use of sublingual, ginal properties. It is unlikely to be useful for definitive topical or IV nitroglycerin infusion is recommended management of hypertensive emergencies or urgencies as a first line agent in blood pressure control in acute due to short duration of action and variable absorption. hypertensive pulmonary oedema and in acute coronary However, its convenient use, ease of administration and rapid onset of action make it an ideal agent for rapid blood pressure control until definitive therapy is com - *Correspondence: dissanayakeha@gmail.com menced in the emergency department or in pre-hospital University Medical Unit, National Hospital of Sri Lanka, Colombo, Sri Lanka setting. There are no studies describing this utility of Full list of author information is available at the end of the article © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/ publi cdoma in/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Prasanna et al. BMC Res Notes (2018) 11:355 Page 2 of 3 sublingual nitroglycerin. We analysed data from a clini- Table 1 Clinical presentations of  hypertensive emergencies (N = 37) cal audit to assess the effectiveness of sublingual nitro - glycerin spray, as a bridging option during the inevitable Presentation Number Percentage (%) delay in setting up IV nitroglycerin. of patients Pulmonary oedema 16 43.2 Main text Acute coronary syndrome 7 18.9 Methods Neurological symptoms/signs 14 37.9 Design and setting (excluding stroke) A clinical audit was conducted at the emergency depart- ment of a tertiary care centre in Sri Lanka from August, 2017 to December, 2017. Patients presenting with hyper- Table 2 shows the blood pressure on admission and the tensive emergencies who required intravenous nitro- reductions in blood pressure 5 and 10  min after sublin- glycerin administration were selected by convenient gual nitroglycerin. Rapid blood pressure reduction was sampling. achieved with single puff of sublingual nitroglycerin spray. Only one patient had over-reduction of MAP more Selection of participants than 25% at 5  min (28%), which improved to 22% at Inclusion criteria were severe hypertension (defined as 10 min, while another patient who had 18% reduction at systolic blood pressure 180 mmHg or more and/or dias- 5 min had further reduced MAP by 29.5% at 10 min. tolic blood pressure 120  mmHg or more) with evidence Minimum delay from decision to commence IV nitro- of end organ dysfunction. Presence of clinical features glycerin to commencement of therapy was 15 min (mean of heart failure (dyspnoea, orthopnoea, bibasal crackles, 27  min) and was due to delays in gaining IV access and hypoxia SpO2 < 94% in the absence of chronic lung dis- preparation and setting up of the solution for infusion. ease), or angina with electrocardiographic changes sug- gestive of ischemia or neurological symptoms and/or Discussion signs (severe headache, visual blurring, altered conscious Rapid and controlled reduction of blood pressure is the level, papilloedema) were considered as evidence for end main aim in management of hypertensive emergencies. organ dysfunction. Suspected or confirmed aortic dissec - Intravenous administration of antihypertensives are tion, intracranial haemorrhage or stroke were excluded required. However, setting up an intravenous infusion from the study as their blood pressure goals and phar- consumes time, during which patient remains sympto- macological preferences are different. All participants matic and may even deteriorate. We observed that mean or next of kin (where patients’ capacity was limited due time taken for commencement of IV infusion from the to the acute illness) provided informed consent prior to time of deciding to treat is 27 min. Fastest time achieved selection. was 15 min. Therefore it is important to have an alternative strategy Observations which can be rapidly administered and could produce Upon diagnosis of hypertensive emergency that require rapid effect. It is not critical for it to be highly efficacious IV nitroglycerin infusion, patients were administered or long lasting as its role is to bridge the time until defini - single puff of nitroglycerin spray sublingually (0.4  mg). tive IV preparation is ready to use. Nitroglycerin sublin- Blood pressure was monitored every 5 min by automated gual spray has the advantages of being easy to administer monitoring machines using arm blood pressure cuff and (without a need for IV access) and having rapid absorp- was confirmed with manual blood pressure measurement tion and onset of action. Therapeutic utility of nitroglyc - with a mercury sphygmomanometer and systolic, dias- erin has been questioned at times due to its venodilatory tolic and mean arterial blood pressures (SBP, DBP and effects, potential to reduce cardiac output and cause MAP respectively) were recorded. Time taken to prepare reflex tachycardia [4]. However one recent study demon - the IV nitroglycerin infusion was noted. Other regular strated effective blood pressure reduction with sublingual medical management was continued unchanged accord- nitroglycerin in hypertensive urgencies [5]. Yet it is not ing to unit protocols. known whether sublingual nitroglycerin could achieve clinically relevant blood pressure reduction for a brief Results duration in a hypertensive emergency. Our analysis was Thirty seven patients met the selection criteria for aimed to answer this question. enrolment. Mean age was 65.6  years and 29 were males Findings of this clinical audit demonstrate that sub- (88.4%). Their clinical presentations are summarized in lingual nitroglycerin is efficacious, rapid in onset and Table 1. Prasanna et al. BMC Res Notes (2018) 11:355 Page 3 of 3 Table 2 Blood pressure on admission and after treatment with sublingual nitroglycerin On admission 5 min after spray 10 min after spray Mean Reduction from baseline Mean Reduction (%) from baseline (%) Systolic BP 217.0 (14.7) 197.8 (13.3) 8.7 188.5 (9.6) 13.1 Diastolic BP 136.2 (9.6) 115.5 (12.6) 15.1 110.3 (9.9) 19.0 Mean BP 163.2 (8.1) 143.0 (9.9) 12.3 136.4 (7.8) 16.3 Blood pressure values are mean (SD). BP blood pressure Author details achieved desired blood pressure control. This is in keep - Emergency Medicine, Post Graduate Institute of Medicine, University ing with its known pharmacokinetic properties, being of Colombo, Colombo, Sri Lanka. University Medical Unit, National Hospital rapidly absorbed through mucous membrane of oral cav- of Sri Lanka, Colombo, Sri Lanka. Department of Clinical Medicine, University of Colombo, Colombo, Sri Lanka. ity. Only one patient experience sustained over correc- tion of blood pressure, exceeding 25% reduction of MAP. Acknowledgements These findings have two important implications. Firstly, We thank the staff of the emergency department for their assistance and all the patients and family who participated in the audit. we suggest that sublingual nitroglycerin spray can be a useful adjunct in the management of a hypertensive Competing interests emergency until parental preparation is prepared, thus The authors declare that they have no competing interests. preventing complications due to unavoidable delays. Sec- Availability of data and materials ondly, this also indicates the potential usefulness of sub- Patient data from the audit are available with the GRC for reference if required. lingual nitroglycerin spray in out-of-hospital setting for Consent for publication paramedical services in better management of hyperten- Not applicable. sive emergencies. Therefore we conclude that sublingual nitroglycerin Ethics approval and consent to participate Data were obtained from a clinical audit and ethical approval was waived by spray is effective in reducing blood pressure in a hyper - the Ethics Review Committee of Asiri Surgical Hosptal according to Health Care tensive emergency, until IV preparation is made available. Quality Improvement Partnership Guide to managing ethical issues in quality We suggest that potential use of sublingual nitroglycerin improvement or clinical audit projects (February 2017). Patients/next of kin provided written informed consent to be included in the audit. in hypertensive emergencies should be studied further, in a larger population, with a control group with prospec- Funding tive follow up to determine final outcome. None. Publisher’s Note Limitations Springer Nature remains neutral with regard to jurisdictional claims in published There are few limitations in our study. Firstly, it is lim - maps and institutional affiliations. ited by small sample size. Secondly, effect of nitroglycerin Received: 10 February 2018 Accepted: 31 May 2018 was not compared against a control or a placebo. Thirdly, effect of early correction of high blood pressure on mor - tality, duration of hospital stay, need for other antihyper- tensives or morbidity were not assessed. Fourthly we did References not observe any adverse effects of therapy probably due 1. Chobanian AV, Bakris GL, Black HR, et al. Joint National Committee on to the good safety profile of this medication and also due Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure to the small sample size that was not adequate to deter- Education Program Coordinating Committee. Seventh Report of the Joint mine more rare adverse events. National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206. 2. Annual Health Bulletein. Ministry of Health. Nutrition and Indigenous Medicine, Abbreviations Sri Lanka. 2015. p. 33–38. http://www.healt h.gov.lk/moh_final /engli sh/publi c/ BP: blood pressure; DBP: diastolic blood pressure; IV: intravenous; MAP: mean elfin der/files /publi catio ns/AHB/2017/AHB%20201 5.pdf . Accessed 2 Jan 2018. arterial pressure; SBP: systolic blood pressure. 3. Tintinalli J, Stapczynski J, Ma O, Yealy D, Meckler G, Cline D. Tintinalli’s emer- gency medicine. New York: McGraw-Hill Education; 2016. p. 399–405. Authors’ contributions 4. Varon J, Marik PE. Clinical review: the management of hypertensive crisis. GRC conceived the concept and research question, designed and conducted Crit Care. 2003;7(5):374–84. https ://doi.org/10.1186/cc235 1. the audit. NP reviewed literature and collected data. NP and HAD analysed 5. Maleki A, Sadeghi M, Zaman M, Tarrahi MJ, Nabatchi B. Nifedipine, cap- data and prepared the manuscript. All authors read and approved the final topril or sublingual nitroglycerin, which can reduce blood pressure the manuscript. most? ARYA Atheroscler. 2011;7(3):102–5.

Journal

BMC Research NotesSpringer Journals

Published: Jun 5, 2018

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