Date: September 25th, 2019

Reference: Bath PM et al. Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomized, sham-controlled, blinded, phase 3 trial. The Lancet March 2019.

Guest Skeptic: Clay Odell is a Paramedic/RN for New London Hospital EMS in New Hampshire, USA which provides 9-1-1 coverage and Mobile Integrated Healthcare for seven rural communities. He’s been involved in EMS for over 30 years in a variety of roles and is a strong advocate for evidence-based EMS protocols.

Case: Your ambulance responds to a 9-1-1 call for a 75-year-old male experiencing abrupt onset of left sided weakness. You arrive to find the patient awake and alert, with a facial droop, slurred speech and left-sided arm drift (FAST-ED score = 3). He has a history of hypertension. His vital signs are heart rate 90 beats per minute, blood pressure 162/96 mmHg, respiratory rate 14 breaths per minute, SpO2 96% on room air, capillary blood glucose 120 mg/dl (6.7 mmol/L). His 12-lead ECG shows a normal sinus rhythm without ST abnormality or ectopy. While preparing for transport you contemplate administering nitroglycerin due to the likelihood of stroke.

Background: We have covered stroke many times on the SGEM (SGEM#29: Stroke Me, Stroke Me; SGEM#70: The Secret of NINDS; SGEM Xtra:Thrombolysis for Acute Stroke; SGEM Xtra: No Retreat, No Surrender; and SGEM Xtra: The Walk of Life). This episode will not debate the use of tPA for acute ischemic stroke. Rather we will be discussing whether lowering the blood pressure of a patient suspected of having a stroke in the pre-hospital setting will have a net beneficial patient-oriented outcome (POO).

Hypertension is common in acute stroke and is a predictor of poor outcome [1]. There is still some controversy on whether or not it is beneficial to lower the blood pressure in these cases [2].

Previous studies suggested that Nitric Oxide (NO) donors, such as transdermal glyceryl trinitrate (GTN – also known as nitroglycerin), reduced blood pressure, improved cerebral blood flow and reduced stroke lesion size if administered early [3 and 4].

There have been five randomized trials looking at nitroglycerin with four not showing superiority for functional outcome. One phase 2 trial done in the pre-hospital setting (RIGHT: Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial) did suggest a benefit to nitroglycerine [5].

The RIGHT study was a subgroup analysis of the ENOS (Efficacy of Nitric Oxide in Stroke) that looked at nitroglycerin within 6 hours of stroke. It too failed to demonstrate a statistical benefit [6].

However, a SRMA of individual patient data in these five trials suggested that earlier administration of nitroglycerin was associated with better outcomes in both ischemic and intracerebral hemorrhage stroke. It also was associated with lower mortality, disability, cognitive impairment, mood disturbance and poor quality of life (QOL) [7].

The conclusion to the RIGHT study was that a larger trial is needed to determine if nitroglycerin improves survival with good neurologic outcome.

Clinical Question: Does early administration of glyceryl trinitrate (nitroglycerin) by paramedics in the pre-hospital setting improve neurologic outcom...