High-Dose Nitroglycerin for Sympathetic Crashing Acute Pulmonary Edema

High-Dose Nitroglycerin for Sympathetic Crashing Acute Pulmonary Edema (SCAPE)

Pharmacy Friday Pearl – Pharmacy & Acute Care University

Introduction

SCAPE is a form of hypertensive heart failure triggered by a surge in catecholamines.
The result is pulmonary capillary leakage and alveolar flooding.
Management includes non-invasive ventilation and pharmacologic agents such as nitroglycerin.
Dose-dependent afterload reduction with nitroglycerin requires doses >50–150 mcg/min.

Pharmacology of Nitroglycerin (NTG)

Parameter	Details
Mechanism of Action	Organic nitrate vasodilator that reduces tension on vascular smooth muscle and dilates peripheral veins and arteries (at higher doses).
Dose	• Chest pain: 5–400 mcg/min (starting at 5 mcg/min) • Pulmonary edema/afterload reduction: 50–400 mcg/min • Titrate to symptom improvement and tolerated blood pressure
Administration	• IV infusion: 50–400 mcg/min until symptom resolution • IV bolus: 400–2000 mcg over 2–5 min (check hospital policy) • Sublingual: 400 mcg tab, 2–4 tablets (≈160–320 mcg/min IV) • Ointment: slow onset 30–60 min
PK/PD	• Onset: IV 1–5 min; SL 1–3 min • Peak: 3–15 min • Duration: IV 5–10 min; SL 10–60 min • Elimination: 22% renal
Adverse Effects	Headache, hypotension, syncope, rebound hypertension, tolerance with prolonged use (~24 hrs)
Warnings/Interactions	• PDE inhibitors • Aortic stenosis, preload-dependent cardiomyopathy, hypertrophic obstructive cardiomyopathy, hypotension at any time
Compatibility	Incompatible with levofloxacin, SMX-TMP, daptomycin, and phenytoin

Clinical pearl: Higher doses of IV or bolus nitroglycerin may reduce ICU admissions and intubation risk in SCAPE.

Overview of Key Evidence

Author/Year	Design (n)	Intervention & Comparison	Key Findings
Patrick, 2020	Observational (n=48)	IV NTG 1 mg bolus by EMS	↓SBP by 31 mmHg, ↓HR by 10 bpm, ↑O2 from 86% to 98%; 2% symptomatic hypotension
Hsieh, 2018	Case Report (n=3)	SL NTG 0.6 mg x 3, IV NTG bolus 1 mg Q2 min, then infusion 40 mcg/min	Normalized respiratory status, avoided intubation & ICU admission
Paone, 2018	Case Report (n=1)	IV NTG 400 mcg/min titrated	Symptom resolution at 6 minutes
Wilson, 2016	Observational (n=395)	IV NTG bolus (500–2000 mcg) Q3–5 min vs infusion vs both	↓ICU admissions, shorter LOS, no increase in intubations
Levy, 2007	Observational (n=29)	IV NTG bolus 2 mg IV Q3 min	↓Intubation, ↓BiPAP/ICU admission
Sharon, 2000	RCT (n=40)	IV isosorbide bolus 4 mg Q4 min vs infusion + BiPAP	↓Intubation, MI, mortality; ↑PaO₂
Cotter, 1998	RCT (n=104)	IV isosorbide bolus 3 mg Q5 min + furosemide vs infusion titration	↓MV & MI, ↑PaO₂, fewer adverse effects

Clinical Conclusions

High-dose nitroglycerin (bolus and/or infusion) is effective in rapidly reducing preload and afterload in SCAPE.
Doses of ≥400 mcg/min (or equivalent bolus) are supported by case reports and observational studies.
High-dose IV or sublingual NTG has been associated with improved respiratory status, fewer ICU admissions, and reduced need for intubation.
Symptomatic hypotension is rare but monitoring is necessary, especially with bolus regimens.
Bolus dosing strategies may outperform continuous infusions in acute SCAPE decompensation.

Full Reference List

Nitroglycerin. Micromedex [Electronic version]. Greenwood Village, CO: Truven Health Analytics. Retrieved March 5, 2020, from http://www.micromedexsolutions.com/
Kramer K. Am Heart J. 2000;140:451–5.
Agrawal N. Crit Care Med. 2016;20:39–43.
Mebazaa A. Eur J Heart Fail. 2015;17:544–58.
Viau DM. Heart. 2015;101:1861–7.
McMurray JJ. Eur J Heart Fail. 2012;14:803–69.
López-Rivera F. Am J Case Rep. 2019 Jan 21;20:83–90.
Clemency BM. Prehosp Disaster Med. 2013 Oct;28(5):477–81.
Yancy CW. J Am Coll Cardiol. 2013;62:e147–239.
Hsieh Y. Turk J Emerg Med. 2018;18(1):34–36.
Wilson SS. Am J Emerg Med. 2017;35(1):126–31.
Levy P. Ann Emerg Med. 2007;50:144–52.
Sharon A. J Am Coll Cardiol. 2000;36(3):832–7.
Cotter G. Lancet. 1998;351(9100):389–93.
Paone S. Am J Emerg Med. 2018;36(8):1526.e5–1526.e7.
Patrick C. Prehosp Emerg Care. 2020 Jan 27:1–7.

The Use of Norepinephrine vs Epinephrine in Post Cardiac Arrest Shock

Pharmacy Friday Pearl – Pharmacy & Acute Care University

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Introduction

The effects of epinephrine on animal hemodynamics have been studied since the late 1800s with recent concern regarding deleterious complications with cerebral and myocardial oxygen supply.
Recently, norepinephrine has been considered post cardiac arrest to minimize complications associated with epinephrine.

Pharmacology of Epinephrine and Norepinephrine

Category	Epinephrine	Norepinephrine
Dose	Weight-based: 0.01–1 mcg/kg/min Non-weight-based: 1–80 mcg/min Institutional infusion rates may vary	Weight-based: 0.05–1 mcg/kg/min (initiate at 0.05–0.15) Non-weight-based: 5–80 mcg/min (initiate at 5–15) Institutional infusion rates may vary
Pharmacokinetics	Onset: Immediate Distribution: 1–2 min to peak Metabolism: hepatic Elimination: urine (inactive metabolites) Half-life: <5 min	Onset: Immediate Distribution: 1–2 min to peak Metabolism: hepatic Elimination: urine (inactive metabolites) Half-life: <5 min
Adverse Effects	Tachyarrhythmias, myocardial ischemia, extravasation leading to necrosis
Mechanism of Action	α agonist → Peripheral vasoconstriction → ↑ myocardial & cerebral blood flow β agonist → ↑ heart rate & contractility → ↑ myocardial oxygen demand
Compatibility	Refer to institutional policies for line compatibility and Y-site administration.

Clinical pearl: Norepinephrine may offer a hemodynamic advantage over epinephrine in certain post-arrest scenarios.

Overview of Key Evidence

Author/Year	Design (n)	Key Findings
Bougouin, 2022	Retrospective (N=766)	Epinephrine group had higher all-cause hospital mortality (OR 2.6; 95% CI 1.4–4.7; P=0.002) and more CPC 3–5 at discharge.
Weiss, 2021	Retrospective (N=93)	EPI group had more refractory hypotension, rearrest, or death in ED (50% vs 22.2%; P=0.008); adjusted odds of adverse events 3.94 times higher (P=0.013).
Mion, 2014	Case report (N=1)	After recurrent VF with epinephrine, transition to norepinephrine led to ROSC and full recovery post ICU stay.
Kim, 2012	Retrospective (N=90)	Survivors were more likely to have received norepinephrine (34.8% vs 22.6%); even more pronounced in prolonged arrest group (42.85% vs 25%).

Clinical Conclusions

It remains controversial whether epinephrine is the preferred vasopressor post-cardiac arrest.
Norepinephrine is a reasonable alternative post-arrest, particularly when adverse effects from epinephrine are of concern.

Full Reference List

Micromedex [Electronic version]. Greenwood Village, CO: Truven Health Analytics. Accessed 2022, March 15. http://www.micromedexsolutions.com/
Callaway C. Epinephrine for cardiac arrest. Current Opinion in Cardiology. 2013;28(1):36-42.
Epinephrine [package insert] Lake Forest, IL: Hospira, Inc.; 2019.
Kim et al. THE BENEFIT OF NOREPINEPHRINE INFUSION FOR HEMODYNAMIC SUPPORT FOLLOWING CARDIOPULMONARY ARREST AND RESUSCITATION. Critical Care Medicine. 2012;40(12):1-328.
Mion G, et al. Cardiac arrest: should we consider norepinephrine instead of epinephrine? Am J Emerg Med. 2014;32(12):1560.e1-2. PMID: 24997106.
Weiss A, et al. Comparison of Clinical Outcomes with Initial Norepinephrine or Epinephrine for Hemodynamic Support After Return of Spontaneous Circulation. Shock. 2021;56(6):988-993. PMID: 34172611.
Bougouin W, et al. Epinephrine versus norepinephrine in cardiac arrest patients with post-resuscitation shock. Intensive Care Med. 2022;48(3):300-310. PMID: 35129643.

Procainamide for Wide Complex Tachycardia

Pharmacy Friday Pearl – Pharmacy & Acute Care University

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Introduction

Ventricular tachycardia (VT) is an uncommon but dangerous medical condition with an extremely variable clinical presentation.
Intravenous procainamide is guideline recommended and is the drug of choice for hemodynamically stable VT with a class IIa recommendation.
Procainamide is an old drug with new evidence supporting its use, but dosing strategies and administration techniques make it difficult to use at the bedside.

Procainamide

Parameter	Details
Bolus Dose	10–17 mg/kg over 20–60 minutes (Max dose 1g, max rate 20–50 mg/min) OR 100 mg every 5 minutes (max rate 50 mg/min) up to 1g
Renal Adjustments	eCrCl 10–50 ml/min: reduce dose by 25–50% eCrCl <10 ml/min: reduce dose by 50–75%
Maintenance Infusion	1–6 mg/min
Mechanism	Class 1A anti-arrhythmic; blocks fast sodium channels, prolongs action potential, reduces impulse conduction speed
PK/PD	IV Onset: <2 min; IM: 10–30 min IV Peak: 25–60 min; IM: 15–60 min Duration: 3–4 hrs Metabolism: Hepatic to active NAPA Half-life: 2.5–4.7 hrs (NAPA: 7 hrs) Excretion: 40–70% renally unchanged
Adverse Effects	Hypotension, hepatotoxicity, lupus-like syndrome, positive ANA, anaphylaxis (sulfite), MG exacerbation, angioedema
Drug Interactions	Interacts with diazepam, diltiazem, milrinone, phenytoin, hydralazine
Compatibility	Compatible: 0.9% NaCl, 0.45% NaCl Incompatible: D5 (variable), LR, D5NS

Clinical Pearl: Define institutional dosing and administration policies due to variable strategies in the literature and risk of adverse events.

Overview of Key Evidence

Author/Year	Design (n)	Key Findings
Ortiz, 2017	RCT (n=62)	Procainamide: 67% VT termination; 9% major cardiac adverse Amiodarone: 38% VT termination; 41% adverse
Marill, 2010	Multicenter cohort (n=187)	VT termination: Amio 25%, Procainamide 30%
Komura, 2010	Retrospective (n=90)	Procainamide terminated 75.7% VT vs. Lidocaine 35%
Marill, 2006	Case series (n=33)	Amio VT termination: 29%; 6% needed cardioversion
Gorgels, 1996	Randomized (n=79)	Procainamide terminated 79% VT vs. Lidocaine 19% (p<0.001)
Callans, 1992	Observational (n=15)	VT termination rate 93% with median 600 mg procainamide

Clinical Conclusions

Procainamide is guideline-supported for stable VT (Class IIa).
Use empiric 10–17 mg/kg bolus dosing up to 1g.
Consider renal function for bolus dose reductions.
Initiate maintenance infusion at 1–6 mg/min after bolus.
Clearly define hospital protocols to avoid variability.

Full Reference List

Procainamide. Micromedex [Electronic version]. Greenwood Village, CO: Truven Health Analytics. Retrieved July 6, 2020, from http://www.micromedexsolutions.com/
Long B, Koyfman A. Best Clinical Practice: Emergency Medicine Management of Stable Monomorphic Ventricular Tachycardia. J Emerg Med. 2017;52:484-492.
Ortiz M, Martín A, Arribas F, et al. Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: the PROCAMIO study. Eur Heart J. 2017;38(17):1329-1335.
Marill KA, deSouza IS, Nishijima DK, et al. Amiodarone or procainamide for the termination of sustained stable ventricular tachycardia: an historical multicenter comparison. Acad Emerg Med. 2010;17(3):297-306.
Komura S, Chinushi M, Furushima H, et al. Efficacy of procainamide and lidocaine in terminating sustained monomorphic ventricular tachycardia. Circ J. 2010;74(5):864-869.
Marill KA, deSouza IS, Nishijima DK, et al. Amiodarone is poorly effective for the acute termination of ventricular tachycardia. Ann Emerg Med. 2006;47(3):217-224.
Gorgels AP, van den Dool A, Hofs A, et al. Comparison of procainamide and lidocaine in terminating sustained monomorphic ventricular tachycardia. Am J Cardiol. 1996;78(1):43-46.
Callans DJ, Marchlinski FE. Dissociation of termination and prevention of inducibility of sustained ventricular tachycardia with infusion of procainamide: evidence for distinct mechanisms. J Am Coll Cardiol. 1992;19(1):111-117.
Wellens HJ, Bär FW, Lie KI, et al. Effect of procainamide, propranolol and verapamil on mechanism of tachycardia in patients with chronic recurrent ventricular tachycardia. Am J Cardiol. 1977;40(4):579-585.

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PACULit Newsletter July 2025 (3 of 4)

PACULit Newsletter - July 2025

PACULit

High-Impact Studies Review — July 2025 (3/4)

Stay updated with breakthrough research in emergency medicine, critical care, and advanced therapeutics.

Featured Educational Video

In this clinical dive from PACUPod, we explore three timely studies changing how we approach critical care, sepsis, and cardiac arrest. First up, we examine a bold randomized trial testing whether ultra-high doses of esomeprazole can reduce inflammation in septic patients. Despite the pharmacologic promise, the results show no reduction in organ dysfunction or inflammatory markers—reminding us that more isn't always better. Next, we break down the hemodynamic physiology of out-of-hospital cardiac arrest from the AMCPR trial. This study reveals that diastolic blood pressure, more than ETCO₂, strongly predicts return of spontaneous circulation—spotlighting real-time metrics that may guide resuscitation strategies in the field. Finally, we look at whether adding lactate to the qSOFA score (LqSOFA) enhances risk stratification for septic patients in the ED. The answer? A solid yes, with better sensitivity for identifying patients who will need ICU care, vasopressors, or who are at risk of death—though specificity takes a small hit. These are insights you can use on your next shift—evidence-based, fast-paced, and practice-changing.

1. A Multinational Randomized Trial of Mega-Dose Esomeprazole As Anti-Inflammatory Agent in Sepsis

Critical Care Medicine | 2025

This double-blind trial enrolled 307 adults with sepsis/septic shock across 17 ICUs/EDs, comparing 72 h of high-dose esomeprazole (1024 mg) versus placebo on organ-dysfunction outcomes.

Key Findings

No SOFA Improvement: Median mean daily SOFA to day 10 was identical (5; IQR 3-9 vs 3-8; p>0.99).
Neutral Secondary Outcomes: ICU-free days, antibiotic-free days, and 28-day mortality were unchanged.
Mechanistic Sub-Study: Ex vivo monocyte cytokine responses were unaffected, disputing an anti-inflammatory benefit.

Clinical Pharmacist's Perspective

High-dose PPI therapy should not be pursued for immunomodulation in sepsis; prioritize proven bundle elements (early antibiotics, source control) and reserve PPIs for GI bleeding prophylaxis.

Full Article

2. Diastolic Blood Pressure & End-Tidal CO₂ During CPR and Outcomes: Secondary Analysis of the AMCPR Trial

Resuscitation | 2025

Among 264 adult out-of-hospital cardiac arrest patients, investigators correlated early CPR hemodynamics with sustained return of spontaneous circulation (ROSC).

Key Findings

DBP Predicts Success: Follow-up DBP >26.5 mmHg (≈10 min) yielded aOR 10.0 for sustained ROSC.
Delta DBP Matters: Raising DBP by >6.5 mmHg doubled ROSC likelihood (aOR 4.8).
ETCO₂ Less Informative: ETCO₂ values were largely similar between groups except at follow-up, indicating DBP is the stronger physiologic target.

Clinical Pharmacist's Perspective

Encourage teams to monitor DBP (e.g., arterial line or Doppler) and titrate compression quality/vasopressors to maintain >26 mmHg; stock ready-to-push epinephrine/norepinephrine to achieve perfusion pressures.

Full Article

3. Initial Lactate-Augmented qSOFA (LqSOFA) in Emergency Department Sepsis

American Journal of Emergency Medicine | 2025

This retrospective cohort of 1,274 suspected sepsis patients compared LqSOFA (qSOFA+ initial lactate) against standard qSOFA for predicting ICU admission, vasopressor need, and 72-h mortality.

Key Findings

Higher Sensitivity: LqSOFA better identified patients needing ICU (48 % vs 30 %), pressors (68 % vs 50 %), and those who died (76 % vs 71 %).
Trade-Off in Specificity: Specificities were lower for LqSOFA (e.g., mortality 67 % vs 80 %).
Superior AUROC for Mortality: LqSOFA showed a statistically greater AUC for death prediction (p<0.05).

Clinical Pharmacist's Perspective

Advocate point-of-care lactate testing with triage; LqSOFA can flag high-risk patients sooner, but balance earlier escalation against false positives and resource strain.

Full Article

🔎 Final Takeaways:

No Benefit from Mega-Dose Esomeprazole: High-dose PPI therapy failed to improve organ dysfunction in sepsis—stick to guideline-directed care.
Target DBP >26 mmHg During CPR: Diastolic pressure outperforms ETCO₂ as a hemodynamic goal for ROSC in OHCA.
LqSOFA Beats qSOFA for Early Sepsis Risk: Adding lactate boosts sensitivity and AUROC, aiding rapid triage—accepting some loss of specificity.

PACULit Newsletter - March 14, 2025

PACULit

High-Impact Studies Review — May 2025

Stay updated with breakthrough research in emergency medicine, critical care, and advanced therapeutics.

Featured Educational Video

In this high-impact episode of PACUPod, we break down five critical studies reshaping emergency and critical care. From the ripple effects of the 2024 IV fluid shortage on ED operations to the potential of Nirsevimab in reducing pediatric ICU admissions, we dive deep into how the latest data is influencing frontline practice. We also explore compelling evidence for rescue ketamine in prehospital status epilepticus, the role of prothrombin complex concentrate for anticoagulated patients with mild TBI, and new insights into arginine vasopressin’s hemodynamic effects in septic shock. Whether you're on shift or between cases, this is your evidence-based update—fast, focused, and clinically relevant.

1. The Impact of the 2024 Intravenous Fluid Shortage on Emergency Department Length of Stay and 72-Hour Return Rate

Critical Care Medicine | 2025

This study examines the consequences of the 2024 intravenous (IV) fluid shortage on emergency department (ED) operations, focusing on patient length of stay and 72-hour return rates.

Key Findings

Increased ED Length of Stay: Patients experienced longer stays due to fluid shortages.
Higher 72-Hour Return Rates: More patients returned to the ED within 72 hours, indicating unresolved symptoms.
Critical Impact on Supply Chain Management: Highlights the need for robust inventory management strategies.

Clinical Pharmacist's Perspective

Support proactive supply chain management and optimize fluid therapy to prevent adverse patient outcomes during shortages.

Full Article

2. Nirsevimab Prophylaxis on Pediatric Intensive Care Hospitalization for Severe Acute Bronchiolitis

Annals of Intensive Care | 2025

This study evaluates the impact of administering Nirsevimab, a monoclonal antibody targeting the respiratory syncytial virus (RSV), as a prophylactic treatment in neonates.

Key Findings

Reduced PICU Admissions: Nirsevimab significantly lowered the rate of PICU admissions for severe bronchiolitis.
Cost-Effective Prophylaxis: Reduced healthcare costs due to lower PICU utilization.
Safe Administration: Minimal adverse effects observed, making it a safe option for prophylaxis.

Clinical Pharmacist's Perspective

Ensure appropriate use of Nirsevimab, monitor for adverse effects, and educate caregivers on RSV prevention to optimize outcomes.

Full Article

3. Evidence Mounts Backing Rescue Ketamine for Prehospital Status Epilepticus

ACEP Now | 2025

This article highlights the use of ketamine as a rescue therapy for midazolam-resistant status epilepticus in prehospital settings.

Key Findings

Effective Seizure Control: Ketamine provided rapid seizure control when midazolam failed.
Multiple Administration Routes: Ketamine was effective via IV, IO, IM, or IN routes.

Clinical Pharmacist's Perspective

Ketamine is considered an essential option for rescue therapy in benzodiazepine-resistant status epilepticus, offering rapid seizure control.

Full Article

4. Systematic Vitamin K Antagonist Reversal with Prothrombin Complex Concentrate in Mild Traumatic Brain Injury

European Journal of Emergency Medicine | 2025

This study examines the impact of using 4F-PCC for rapid reversal of VKAs in patients with mild TBI, reducing hemorrhage progression.

Key Findings

Reduced Hemorrhage Progression: 4F-PCC minimized intracranial bleeding risks.
Improved Recovery: Patients showed better outcomes with rapid VKA reversal.

Clinical Pharmacist's Perspective

4F-PCC is crucial for rapid VKA reversal in TBI patients, ensuring effective hemostasis and better recovery.

Full Article

5. Hemodynamic Effects of Adjunct Arginine Vasopressin to Norepinephrine in Septic Shock

Annals of Intensive Care | 2025

This study investigates the hemodynamic effects of adjunctive arginine vasopressin to norepinephrine in septic shock, identifying factors associated with patient response.

Key Findings

79% Response Rate: Patients showed significant hemodynamic improvement with AVP.
Negative Predictors: Obesity and hyperlactatemia were linked to reduced response.
Positive Predictors: Higher norepinephrine infusion rates correlated with better response.

Clinical Pharmacist's Perspective

AVP is a valuable adjunct in septic shock, but response may vary. Pharmacists should evaluate patient factors to optimize therapy.

Full Article

🔎 Final Takeaways:

IV Fluid Shortage: Highlights the need for proactive inventory management to prevent care disruptions in emergencies.
Nirsevimab Prophylaxis: Demonstrates reduced PICU admissions and cost-effectiveness for severe bronchiolitis prevention.
Rescue Ketamine: Provides effective seizure control for midazolam-resistant status epilepticus in prehospital settings.
VKA Reversal with 4F-PCC: Ensures rapid reversal of anticoagulation in mild TBI, reducing hemorrhage risks.
AVP in Septic Shock: Effective in improving hemodynamics, but patient response varies based on specific factors.

High-Dose Nitroglycerin for Sympathetic Crashing Acute Pulmonary Edema (SCAPE)

Introduction

Pharmacology of Nitroglycerin (NTG)

Overview of Key Evidence

Clinical Conclusions

Full Reference List

The Use of Norepinephrine vs Epinephrine in Post Cardiac Arrest Shock

Introduction

Pharmacology of Epinephrine and Norepinephrine

Overview of Key Evidence

Clinical Conclusions

Full Reference List

Procainamide for Wide Complex Tachycardia

Introduction

Procainamide

Overview of Key Evidence

Clinical Conclusions

Full Reference List

High-Impact Studies Review — July 2025 (3/4)

Key Findings

Clinical Pharmacist's Perspective

Key Findings

Clinical Pharmacist's Perspective

Key Findings

Clinical Pharmacist's Perspective

High-Impact Studies Review — June 2025 (1/4)

Key Findings

Clinical Pharmacist's Perspective

Key Findings

Clinical Pharmacist's Perspective

Key Findings

Clinical Pharmacist's Perspective

High-Impact Studies Review — May 2025

Key Findings

Clinical Pharmacist's Perspective

Key Findings

Clinical Pharmacist's Perspective

Key Findings

Clinical Pharmacist's Perspective

Key Findings

Clinical Pharmacist's Perspective

Key Findings

Clinical Pharmacist's Perspective