Efficacy of Neuroinvasive Goal-Directed Therapy in Hypoxic Ischemic Brain Injury After Cardiac Arrest
By Vibhu Sharma, MD
Associate Professor of Medicine, University of Colorado, Denver
SYNOPSIS: This retrospective observational study found the suggestion of favorable neurological outcomes at six months among out-of-hospital cardiac arrest patients who received interventions to optimally manage intracranial pressure and brain tissue oxygenation compared to standard care.
SOURCE: Fergusson NA, Hoiland RL, Thiara S, et al. Goal-directed care using invasive neuromonitoring versus standard of care after cardiac arrest: A matched cohort study. Crit Care Med 2021;49:1333-1346.
The investigators in this study tested the hypothesis that invasive management of hypoxic ischemic brain injury (HIBI) after cardiac arrest would lead to improved neurologic outcomes. This was a retrospective, matched, observational cohort study performed at a single center, enrolling adult patients admitted to the intensive care unit (ICU) after a cardiac arrest lasting at least 10 minutes (median, 21 minutes). Most patients had a pulseless electrical activity (PEA) cardiac arrest (~80% in both groups), with a minority having shockable rhythms. Patients were enrolled within 72 hours of return of spontaneous circulation (ROSC) and had a post-resuscitation Glasgow Coma Scale (GCS) score of less than 8. More than 70% in each group were deeply comatose with a GCS of 1. None of the cardiac arrests were inpatients. The median age of patients was 40 years for the intervention group (n = 21) and 58 years for the standard of care group (n = 44).
All patients received targeted temperature management (TTM) consistent with institutional guidelines. The intervention, or goal-directed care (GDC) group, received invasive neuromonitoring; patients were enrolled in this group based on availability of a neurosurgeon to place intracranial devices. Specifically, an intracranial intraparenchymal pressure monitor was placed in the non-dominant frontal lobe to measure intracranial pressure (ICP) and brain tissue oxygenation (PbtO2). In addition, a jugular venous bulb catheter was placed in the dominant internal jugular vein using ultrasound guidance with the tip guided to the mastoid bone. This catheter measured jugular venous oxygen saturation (SjvO2).
Goal-directed therapy targeted PbtO2 of > 20 mmHg and an ICP < 20 mmHg. Interventions aimed at returning PbtO2 to normal included first ensuring ICP was less than 25 mmHg and maintaining mean arterial pressure (MAP) to an acceptable level based on “attending physician discretion” using vasopressors, with norepinephrine being the first choice. Packed red blood cell transfusion was used to bring hemoglobin to 9 g/dL if the previously noted interventions did not optimize PbtO2. Partial pressure of peripheral blood oxygen was maintained between 80 mmHg to 100 mmHg. Body temperature was maintained using guideline-directed targeted temperature management.
With respect to ICP management, a multi-tiered approach was used to maintain ICP < 20 mmHg. An ICP > 20 mmHg for > 10 minutes was actionable. Head of bed elevation to > 30 degrees, optimization of sedation, and maintenance of normocapnia and normonatremia were tier 1 interventions. If ICP remained above 20 mmHg for more than 10 minutes despite these interventions, tier 2 interventions were initiated and included osmotherapy (3 mL/kg to 5 mL/kg bolus of 3% saline and/or 0.25 g/kg to 0.5 g/kg of 20% mannitol) and neuromuscular blockade. Escalation to tier 3 therapies included barbiturate therapy and induction of moderate hypothermia.
The standard of care (SoC) cohort was managed with standard targeted temperature management: 36ºC for 24 hours followed by slow rewarming over 48 hours to 37.5ºC. Normoxemia and normocapnia were maintained. Surface devices (e.g., Arctic Sun) were used for active cooling.
The primary outcome was neurologic outcomes at six months measured using the Cerebral Performance Category (CPC) score; a score of 3-5 is defined as unfavorable and 1-2 as favorable. The CPC was assessed by trained investigators over the phone who called the patient or an authorized representative. Favorable neurologic outcomes were more frequent in the intervention cohort (43%) compared with the standard of care cohort (10%) (P = 0.016). This was driven mostly by the GDC group having a significantly higher MAP (~90 mmHg) and lower temperature over the course of their ICU stay.
COMMENTARY
This study describes an intriguing concept of neuroinvasive management in the care of patients with post-cardiac arrest HIBI. The major factor for allocation to the GDC group was the availability of an attending neurosurgeon. It is possible that the perception of more severe neurological injury may have made it more likely for a neurosurgeon to be called, leading to concern for selection bias. Patients could be enrolled up to 72 hours after ROSC. The authors did not delineate time to intervention with GDC.
It is plausible that early intervention is associated with better outcomes. Most patients in this study were brought to the emergency department with PEA arrest, which typically is associated with worse outcomes than shockable arrests.1 Significantly more patients in the GDC group had unreactive pupils at enrollment (43% vs. 18%, P = 0.045). It is possible that more aggressive therapy in severe HIBI may improve prognosis. Biomarker measurement may help neuro-prognostication2 further, and application of invasive therapies may be triaged to those with higher levels of brain biomarkers in the setting of HIBI.
The duration of cardiac arrest was short and, therefore, longer arrests may not benefit from aggressive therapy. Significantly more arrests in the SoC group were of cardiac etiology than in the GDC group (32% vs. 10%, respectively). All of the patients in this study had an out-of-hospital cardiac arrest, and the benefits (if any) of GDC cannot be assessed for in-hospital cardiac arrests.
All patients with HIBI ought to have aggressive interventions to maintain normothermia. In the absence of invasive monitoring of ICP, point-of-care ultrasound may be used by trained intensivists to assess optic nerve sheath diameter (ONSD), and transcranial Dopplers can assess middle cerebral artery diastolic flow velocities. Both have been shown to correlate well with invasively assessed intracranial pressure.3,4
In the event that a clear benefit for invasive GDC is demonstrated eventually, this intervention may remain aspirational for all but the largest quaternary care medical centers, given the scarcity of qualified neurosurgeons. Larger studies are needed to validate the benefit of early invasive GDC in patients with HIBI after cardiac arrest.
REFERENCES
- Fukuda T, Ohashi-Fukuda N, Matsubara T, et al. Association of initial rhythm with neurologically favorable survival in non-shockable out-of-hospital cardiac arrest without a bystander witness or bystander cardiopulmonary resuscitation. Eur J Intern Med 2016;30:61-67.
- Moseby-Knappe M, Mattsson-Carlgren N, Stammet P, et al. Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest. Intensive Care Med 2021;47:984-994.
- Weidner N, Kretschmann J, Bomberg H, et al. Real-time evaluation of optic nerve sheath diameter (ONSD) in awake, spontaneously breathing patients. J Clin Med 2021;10:3549.
- Cardim D, Griesdale DE, Ainslie PN, et al. A comparison of non-invasive versus invasive measures of intracranial pressure in hypoxic ischaemic brain injury after cardiac arrest. Resuscitation 2019;137:221-228.
This retrospective observational study found the suggestion of favorable neurological outcomes at six months among out-of-hospital cardiac arrest patients who received interventions to optimally manage intracranial pressure and brain tissue oxygenation compared to standard care.
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