Ultraportable Defibrillator !!! Can be it be game changer ?

Defibrillation as option for treatment for cardiac arrest was first described by Zoll et (N Eng J Med. 1952). Zoll et al in his articles mentions that "The purpose of this report is to describe the successful use in 2 patients of a quick, simple, effective and safe method of arousing the heart from ventricular standstill by an artificial, external, electric pacemaker. For the first time it was possible to keep a patient alive during ventricular asystole lasting for hours to days. This procedure may prove valuable in many clinical situations".

Over the years the defibrillators have been evolved from monophasic to biphasic, High energy to low energy defibrillators. Recently a new genration of defibrillators called ultra portable defibrillators have been launched.

 

Ultraportable automated external defibrillators (AEDs) are a new generation of defibrillators that are small, lightweight, easy to carry on one’s person, and affordable for personal and home use. They offer the opportunity to increase AED availability in case of out-of-hospital cardiac arrest (OHCA) and therefore improve outcomes.

Debaty et al did a systemic review on effectiveness of ultra portable automated external defibrillator found no evidence of ultraportable AED device performance, clinical or safety outcomes. There is an urgent need for further research to determine the safety and effectiveness of ultraportable AEDs.

Concerns

• Limitations number of shocks : 20
• Energy: Max 75 J (Manufactures claim its not the energy , its current which is important and they have engineered the device to deliver the same current with lesser energy.)

Guidelines

• ILCOR 2024 states that currently there is insufficient evidence on the clinical effectiveness of ultraportable or pocket AEDs to make a treatment recommendation. 

Conclusion 

• As of now there is no evidence or recommendation for the use of ultraportable defibrillators. Ultraportable Defibrillators are evolving and as more evidences arises they can be a game changer in management  out of hospital cardiac arrest. 

Reference

• Debaty G, Perkins GD, Dainty KN, Norii T, Olasveengen TM, Bray JE; International Liaison Committee on Resuscitation Basic Life Support Task Force. Effectiveness of ultraportable automated external defibrillators: A scoping review. Resusc Plus. 2024 Aug 7;19:100739. doi: 10.1016/j.resplu.2024.100739. PMID: 39219811; PMCID: PMC11362796.

• S.C. Brooks, G.R. Clegg, J. Bray, et al. Optimizing outcomes after out-of-hospital cardiac arrest with innovative approaches to public-access defibrillation: A scientific statement from the international liaison committee on resuscitation Resuscitation, 172 (2022), pp. 204-228

ILCOR 2024 BLS & ACLS Treatment Recommendation

 

BLS

• ILCOR suggests performing chest compressions on a firm surface when this is practical and does not significantly delay the start of chest compressions (weak recommendation, very low–certainty evidence).

• ILCOR suggest activation of the CPR mode to increase mattress stiffness if available for in-hospital cardiac arrest (good practice statement)

• ILCOR suggest EMS implementing dispatcher-assisted public-access AED systems should monitor and evaluate the effectiveness of their system (good practice statement).

• ILCOR suggest the use of real-time audiovisual feedback and prompt devices during CPR in clinical practice as part of a comprehensive quality improvement program for cardiac arrest designed to ensure high-quality CPR delivery and resuscitation care across resuscitation system (weak recommendation, very low–certainty evidence).

ACLS

Oxygen Targets 

• ILCOR recommend the use of 100% inspired oxygen until the arterial oxygen saturation or the partial pressure of arterial oxygen can be measured reliably in adults with ROSC after cardiac arrest in the prehospital setting (strong recommendation, moderate-certainty evidence) and in-hospital setting (strong recommendation, low-certainty evidence).

• Following reliable measurement of arterial oxygen values, ILCOR suggest targeting an oxygen saturation of 94% to 98% or a partial pressure of arterial oxygen of 75 to 100 mm Hg (≈10–13 kPa) in adults with ROSC after cardiac arrest in any setting (good practice statement).

• ILCOR recommend avoiding hypoxemia in adults with ROSC after cardiac arrest in any setting (strong recommendation, very low–certainty evidence).

Blood Pressure

• There is insufficient scientific evidence to recommend a specific blood pressure goal after cardiac arrest. Therefore, we suggest a mean arterial blood pressure of at least 60 to 65 mm Hg in patients after out-of hospital (moderate-certainty to low-certainty evidence) and IHCA (lowcertainty to very low–certainty evidence).

Temperature Control

• ILCOR suggest actively preventing fever by targeting a temperature ≤37.5 ◦C for patients who remain comatose after ROSC from cardiac arrest (weak recommendation, low-certainty evidence). Whether subpopulations of cardiac arrest patients may benefit from targeting hypothermia at 32 ◦C to 34 ◦C remains uncertain.

• Comatose patients with mild hypothermia after ROSC should not be actively warmed to achieve normothermia (good practice statement).

• ILCOR recommend against the routine use of prehospital cooling with rapid infusion of large volumes of cold intravenous fluid immediately after ROSC (strong recommendation, moderate-certainty evidence).

• ILCOR suggest surface or endovascular temperature control techniques when temperature control is used in comatose patients after ROSC (weak recommendation, low-certainty evidence).

• When a cooling device is used, we suggest using a temperature control device that includes a feedback system based on continuous temperature monitoring to maintain the target temperature (good practice statement).

Seizure Prophylaxis 

• ILCOR suggest against the use of prophylactic antiseizure medication in post–cardiac arrest adults (weak recommendation, very low–certainty evidence).

• ILCOR suggest treatment of clinically apparent and electrographic (EEG) seizures in post–cardiac arrest adults (good practice statement).

• ILCOR suggest treatment of rhythmic and periodic EEG patterns that are on the ictal-interictal continuum in comatose post–cardiac arrest adults (weak recommendation, low-certainty evidence).

ECPR

• ILCOR suggest that ECPR may be considered as a rescue therapy for selected adults with out-of-hospital or in hospital cardiac arrest when conventional cardiopulmonary resuscitation is failing to restore spontaneous circulation in settings where this can be implemented (weak recommendation, low-certainty evidence).

Pregnancy 

• ILCOR suggest delivery of the fetus by perimortem cesarean delivery for women in cardiac arrest in the second half of pregnancy (weak recommendation, very low–certainty evidence).There is insufficient evidence to define a specific time interval by which delivery should begin.There is insufficient evidence to make a recommendation about the use of left-lateral tilt or uterine displacement during CPR in the pregnant patient.

• ECPR may be considered as a rescue therapy for selected cardiac arrest patients during pregnancy or in the postpartum period when conventional CPR fails and in settings in which it can be implemented(good practice statement).

Difficult Airway

• In adults in cardiac arrest, when standard airway management strategies (eg, oropharyngeal airway and bag-mask, supraglottic airway, or tracheal tube) have failed, it is reasonable for appropriately trained rescuers to attempt front-of-neck airway access using a cricothyroidotomy technique (good practice statement).

 

Reference

• 2024 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forceshttps://www.ahajournals.org/doi/10.1161/CIR.0000000000001288

Steroids & CAP

Use of steroids in CAP is highly debated topic for a long time. Recent evidences in this field sheds answers to this question. 

 

CAPE-COD (NEJM.2023) Trial is a multicenter, double-blind, placebo-controlled trial in 31 French ICUs evaluating 200 mg/day infusion of hydrocortisone for 8 or 14 days with a planned taper in patients admitted in ICU with severe non-viral CAP. Yet the trial was stopped early due to the COVID-19 pandemic, the authors reported a significant decrease in mortality, with 6.2% of the hydrocortisone group and 11.9% of the placebo group dead at 28 days (absolute difference −5.6% [95%CI: −9.6 to −1.7%], p = 0.006). In subgroup analyses of the CAPE COD trial, hydrocortisone was most effective in inflammatory patients with CRP > 150 mg/L (relative risk −7.4, [95%CI −12.9−1.7%]

ESCAPe (Intensive Care Med. 2022) is a randomized 586 critically ill patients in 42 American hospitals to receive 40 mg/day of methylprednisolone or placebo for 20 days with a tapering plan within 72–96 h of hospital presentation and observed no significant difference in 60-day mortality (16% vs. 18% [95%CI: -8−5%], p = 0.61) or any other secondary outcomes.

DEXA-ARDS (Lancet.2020), a randomized multicenter study involving 17 ICUs in Spain, showed an increase of 4.8 ventilator-free days ([95%CI: 2.5–7.03], p < 0001) within 28 days in the intervention arm as well as a decreased mortality rate. Patients in the dexamethasone group received an intravenous dose of 20 mg once daily from day 1 to day 5, which was reduced to 10 mg once daily from day 6 to day 10. Early administration of dexamethasone could reduce duration of mechanical ventilation and overall mortality in patients with established moderate-to-severe ARDS.

 

Torres et al (JAMA.2015) did multicentric, double blinded RCT to assess the effect of corticosteroids in patients with severe community-acquired pneumonia and high associated inflammatory response. Patients were randomized to receive either an intravenous bolus of 0.5 mg/kg per 12 hours of methylprednisolone (n = 61) or placebo (n = 59) for 5 days started within 36 hours of hospital admission. Corticosteroid treatment reduced the risk of treatment failure (odds ratio, 0.34 [95% CI, 0.14 to 0.87]; P = .02). In-hospital mortality did not differ between the 2 groups (6 patients [10%] in the methylprednisolone group vs 9 patients [15%] in the placebo group; P = .37)

 

Mechanism of steroids in CAP 

• Recent studies have shown that steroids are beneficial when started early in severe CAP. This can be explained its action on glucocorticoid receptors.

 

• Glucocorticoid Receptors (GR)  is a transcription factor expressed in most cells. After binding steroids, the GR translocates to the nucleus and exerts both genomic and non-genomic effects (notably in mitochondria). During inflammation, epigenetic modifications alter the possibility for GR to regulate the transcription of inflammatory genes. During the first hours of inflammation, steroids reduce inflammatory cytokine production, neutrophils, and T cell recruitment and adhesion . In later days, steroids can have opposite effects on the inflammatory response by reducing anti-inflammatory cytokines secretion or increasing phagocytic capacity.

 

Current Guidelines in CAP

• ATS 2019  don't recommend routine use of Steroids in non severe or severe pneumonia. Steroids can be used in CAP for refractory shock.  
• ERS/ESICM 2023 Guidelines state that in patients with sCAP, we suggest the use of corticosteroids if shock is present.

Conclusion 

• Present guidelines recommends steroids in CAP only for refractory shock, but from recent evidence it may be reasonable for early administration of steroids in severe bacterial pneumonia . Further studies are required to confirm these findings.

Reference

• Bouras M, Rello J, Roquilly A. Steroids in severe community-acquired pneumonia: dangerous, worthless, or miracle cure? The roller coaster of clinical trials. Anaesth Crit Care Pain Med. 2023 Aug;42(4):101253. doi: 10.1016/j.accpm.2023.101253. Epub 2023 May 26. PMID: 37245688; PMCID: PMC10214762.

  
   

Land Mark Trial in Thrombolysis for AIS

Below is a compilation of landmark studies in the field of thrombolysis in acute ischemic stroke .

NINDS (NEJM.1995) is a double blinded RCT done to assess the rTPA. Study proved that despite an increased incidence of symptomatic intracerebral hemorrhage, treatment with intravenous t-PA within three hours of the onset of ischemic stroke improved clinical outcome at three month.

ECASS (JAMA. 1995) a multicentric, double blind RCT  done to evaluate the efficacy and safety of intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke.Intravenous thrombolysis in acute ischemic stroke is effective in improving some functional measures and neurologic outcome in a defined subgroup of stroke patients with moderate to severe neurologic deficit and without extended infarct signs on the initial CT scan. However, the identification of this subgroup is difficult and depends on recognition of early major CT signs of early infarction.

ECASS II (Lancet. 1998) multicentric,placebo controlled,  double blinded, RCT done to assess the safety and efficacy if rTPA within 6hours of onset.The results do not confirm a statistical benefit for alteplase. However, we believe the trend towards efficacy should be interpreted in the light of evidence from previous trials. 

ATLANTIS Trial - Part A (Stroke. 2000 ) was done focusing on evaluating the safety and efficacy of rtPA given between 0 and 6 hours after stroke onset.This study found no significant rtPA benefit on any of the planned efficacy end points at 30 and 90 days in patients treated between 0 and 6 hours after stroke onset. These negative results apply to patients treated after 3 hours, because only 15% of the patients were enrolled before 3 hours. The risk of symptomatic intracerebral hemorrhage was increased with rtPA treatment, particularly in patients treated between 5 and 6 hours after onset. These results do not support the use of intravenous rtPA for stroke treatment >3 hours after onset.

ATLANTIS Trial - Part B (JAMA.1999) was done to test the efficacy and safety of rt-PA in patients with acute ischemic stroke when administered between 3 and 5 hours after symptom onset. This study found no significant rt-PA benefit on the 90-day efficacy end points in patients treated between 3 and 5 hours. The risk of symptomatic ICH increased with rt-PA treatment. These results do not support the use of intravenous rt-PA for stroke treatment beyond 3 hours.

ATLANTIS Trial  (Stroke 2002) (Prespecified subgroup analysis)they evaluated 61 patient in ATLANTIS Study group received rTPA within 3 hours. Study also found that despite a significant increase in the rate of symptomatic intracranial hemorrhage, tPA-treated patients were more likely to have a very favorable outcome (score of
1) on the National Institutes of Health Stroke Scale at 90 days. 

ECASS III(N ENGL J MED. 2008) tested the efficacy and safety of alteplase administered between 3 and 4.5 hours after the onset of a stroke.Study found that As compared with placebo, intravenous alteplase administered between 3 and 4.5  hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke; alteplase was more frequently associated with symptomatic intracranial hemorrhage.

ATTEST Trial (2015) is a randomised, open label, blinded end point done to assess the efficacy and safety of tenecteplase (0.25 mg/kg) versus alteplase (0.9 mg/kg) within 4·5 h of stroke onset in a population not selected on the basis of advanced neuroimaging, and to use imaging biomarkers to inform the design of a definitive phase 3 clinical trial.The study found that there was no significant difference was noted for percentage of pneumbra salvaged 68% for tenecteplase and 68% for alteplase group. Serious adverse events didnot differ in both groups.

MRCLEAN (N ENGL J MED. 2015)  is a multicentric RCT done to assess the effect of intraaterial thrombolysis.In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intraarterial treatment administered within 6 hours after stroke onset was effective and safe. 

NOR-TEST (2017) is a randomised, open label, blinded end point done in 13 stroke units in Norway. It is done to investigate safety and efficacy of tenecteplase (0.4 mg/kg) v/s alteplase (0.9mg/kg) in patients with acute stroke presenting within 4.5h  (n=1100. Primary outcome defined as mRS score 0-1 at 3 months was achieved in 64% in tenecteplase group and 63% in alteplase group.Serious adverse events were similar in both groups. Study concluded that tenecteplase was not superior to alteplase and showed similar safety profile.

WAKE-UP Trial (N Engl J Med 2018) is a multicentric RCT done to determine whether patients with stroke with an unknown time of onset and features suggesting recent cerebral infarction on magnetic resonance imaging (MRI) would benefit from thrombolysis with the use of intravenous alteplase.In patients with acute stroke with an unknown time of onset, intravenous alteplase guided by a mismatch between diffusion-weighted imaging and FLAIR in the region of ischemia resulted in a significantly better functional outcome and numerically more intracranial hemorrhages than placebo at 90 days.

EXTEND-1A TNK  (Int J Stroke. 2018) assessed the reperfusion efficacy of tenecteplase and alteplase in subgroups based on these characteristics in a pooled analysis of the EXTEND-IA TNK trial. Study concluded that tenecteplase demonstrates superior early reperfusion versus alteplase in lesions with low clot burden. Reperfusion efficacy remains limited in internal carotid artery occlusions and lesions with high clot burden. 

EXTEND Trial (N Engl J Med 2019) is a multicenter, randomized, placebo-controlled trial involving patients with ischemic stroke who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging. The patients were randomly assigned to receive intravenous alteplase or placebo between 4.5 and 9.0 hours after the onset of stroke or on awakening with stroke (if within 9 hours from the midpoint of sleep).The trial found that use of alteplase between 4.5 and 9.0 hours after stroke onset or at the time the patient awoke with stroke symptoms resulted in a higher percentage of patients with no or minor neurologic deficits than the use of placebo.

EXTEND-IA TNK Part II (JAMA.2020)To determine whether 0.40 mg/kg of tenecteplase safely improves reperfusion before endovascular thrombectomy vs 0.25 mg/kg of tenecteplase in patients with large vessel occlusion ischemic stroke. The study suggest that the 0.40-mg/kg dose of tenecteplase does not confer an advantage over the 0.25-mg/kg dose in patients with large vessel occlusion ischemic stroke.

NORTEST 2 Part-A (Lancet. 2022). The NOR-TEST trial showed that 0·4 mg/kg tenecteplase had an efficacy and safety profile similar to that of a standard dose (0·9 mg/kg) of alteplase, albeit in a patient population with a high prevalence of minor stroke. The aim of NOR-TEST 2 was to establish the non-inferiority of tenecteplase 0·4 mg/kg to alteplase 0·9 mg/kg for patients with moderate or severe ischaemic stroke. prematurely terminated study (terminated to fulfil the prespecified safety criteria), tenecteplase at a dose of 0·4 mg/kg yielded worse safety and functional outcomes compared with alteplase.

TRACE (Stroke Vasc Neurol. 2022) is a multicentre, prospective, randomised, open-label, blinded end-point, phase II study compared three tiers of 0.1, 0.25, 0.32 mg/kg rhTNK-tPA (to a maximum of 40 mg) with standard 0.9 mg/kg rt-PA (to a maximum of 90 mg) in patients who were eligible for intravenous thrombolysis.Similar to the Caucasians, rhTNK-tPA was well tolerated in Chinese patients with AIS at all doses administered within 3 hours of symptom onset.

ACT Trial (2022) is a multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial  done to determine whether tenecteplase (0.25mg/kg) increase reperfusion compared to alteplase(0.9mg/kg). Study concluded that  IV tenecteplase is a reasonable alternative to alteplase for all patients presenting with AIS.

TWIST Trial (Lancet Neurol. 2023) is aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT. In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging.

TRACE-2 (2023) In this multicentre, prospective, open-label, blinded-endpoint, randomised controlled, non-inferiority trial was done to establish the non-inferiority of tenecteplase to alteplase in AIS.Study found that tenecteplase was non-inferior to alteplase in people with ischaemic stroke who were eligible for standard intravenous thrombolytic but ineligible for or refused endovascular thrombectomy.

TRACE-3 (N Engl J Med 2024) is a randomised trial done in china were patients with large-vessel occlusion of the middle cerebral artery or internal carotid artery who had salvageable brain tissue as identified on perfusion imaging and who did not have access to endovascular thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or standard medical treatment 4.5 to 24 hours after the time that the patient was last known to be well (including after stroke on awakening and unwitnessed stroke). Treatment with tenecteplase administered 4.5 to 24 hours after stroke onset resulted in less disability and similar survival as compared with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage appeared to be higher.

TIMELESS (N Engl J Med 2024) is a multicentric, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well.Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. 

ORIGINAL Trail (JAMA.2024) is a RCT done to determine whether tenecteplase is noninferior to alteplase for patients with acute ischemic stroke (AIS) eligible for intravenous thrombolysis within 4.5 hours after stroke onset.In patients with AIS eligible for intravenous thrombolysis within 4.5 hours after stroke onset, tenecteplase was noninferior to alteplase with respect to excellent functional outcome (mRS score of 0 or 1) at 90 days and had a similar safety profile.