Prehospital administration of glyceryl trinitrate for acute stroke? Not according to this study!
Except for the RIGHT-2 study, pooled analyses of previous studies suggest that very early treatment with glyceryl trinitrate (GTN) of patients with acute ischaemic stroke or intracerebral haemorrhage improves functional outcome. This randomised, open-label, blinded endpoint trial sought to assess whether patients with presumed acute stroke would benefit from GTN commenced within 3 hours of symptom onset. Six ambulance services in the Netherlands recruited eligible adult participants (≥18 years) who had a probable diagnosis of acute stroke (as assessed by a paramedic), a FAST score of 2 or 3, systolic blood pressure of ≥140 mmHg, and could start treatment within 3 hours of symptom onset. Participants were randomly assigned (1:1) by ambulance personnel, to receive either transdermal GTN or standard care alone. The primary outcome was functional outcome assessed with the modified Rankin Scale (mRS) at 90 days. The target sample size was 1400 patients.
The trial was prematurely terminated with only 380 patients randomly allocated to a study group. There were 325 included in the analysis, with 170 assigned to the GTN group and 155 to the control group. In total, 201 patients (62%) had ischaemic stroke, 34 (10%) transient ischaemic attack, 56 (17%) intracerebral haemorrhage, and 34 (10%) a stroke-mimicking condition. In the target population (n=291), the 90-day mRS score was 2 (2–4) in the glyceryl trinitrate group and 3 (1–4) in the control group. There were no differences between the two study groups with respect to death within 90 days or serious adverse events; however, 12 (34%) of 35 patients with intracerebral haemorrhage died within 7 days in the GTN group versus 2 (10%) of 21 in the control group; death within 90 days occurred in 16 (46%) of 35 in the GTN group and 11 (55%) of 20 in the control group. There was no evidence of benefit of transdermal GTN in this study but there was potential for harm to those with intracerebral haemorrhage.
Heads up—this could help to save lives
Despite years of experience, survival following out-of-hospital cardiac arrest (OHCA) remains poor. Conventional cardiopulmoany resuscitation (C-CPR) leads to survival to discharge from hospital in only around 10% of patients. A new approach to resuscitation combines controlled elevation of the head and thorax with active compression decompression (ACD) CPR and an impedance threshold device (ITD). The resuscitation model is known as ACE-CPR and has shown neurologically favourable survival in animal studies, most likely due to decreased intracranial pressure and improved cerebral perfusion pressure and blood flow.
This study assessed the probability of OHCA survival to hospital discharge after ACE-CPR versus C-CPR. As part of a prospective registry study, 227 ACE-CPR OHCA patients were enrolled from six prehospital systems in the United States. Comparative C-CPR patient data (n=5196) were obtained from three large published OHCA randomised controlled trials from high performing prehospital systems. The primary study outcome was survival to hospital discharge with secondary outcomes to include return of spontaneous circulation (ROSC) and favourable neurological survival. The team applied propensity-score matching with a 1:4 ratio to account for imbalances in baseline characteristics between groups.
ACE-CPR (n=222) was associated with higher adjusted odds ratios (OR) of survival to hospital discharge relative to C-CPR (n=860) irrespective of the initial arrest rhythm. Time to initiation was important. When the emergency call to ACE-CPR start time was <10 minutes, the OR of survival to hospital discharge for ACE-CPR was 3.72 (95 % CI: 1.57–8.83) versus C-CPR patients, but this (perhaps unsurprisingly) fell to 1.88 (95 % CI, 1.03–3.44) when time to onset was <18 minutes. Notably, rapid application of ACE-CPR improved the likelihood of ROSC and a favourable neurological survival. Further work is required before ambulance services rush to implement the findings.