Brain injury after non-fatal cardiac arrest
Cardiac arrest occurs in two different settings, in-hospital and out-of-hospital, with completely different prognosis, for obvious reasons.
As cardiac arrests that occur in a hospital context are usually immediately attended, the primary focus of the study of brain injury after cardiac arrest has been among survivors of out-of-hospital cardiac arrest ( OHCA ).
In this setting, brain damage is caused by cerebral hypoperfusion and its severity depends on the time of such deficit; the proportion of cardiac arrest survivors who present with some degree of brain damage ranges from 35% to 100%.
The working group of Chun-Lim and colleagues has delineated three scenarios that are clearly related to the duration of brain hypoperfusion: (i) patients with early recovery of brain function without any sequelae, usually associated with opportune resuscitation and/or early recovery of consciousness ( less than 3 days after OHCA ); (ii) patients with extensive damage, associated with prolonged coma ( more than 7 days after OHCA ); and (iii) an intermediate group between those extremes.
They report that a coma duration of less than 3 days results in a better quality of life at 3- and 12-month follow-up, and that the manifestation of severe cognitive impairment early on in recovery results in higher risk for permanent memory and motor impairment.
Clinical sequelae of brain damage after OHCA may range from mild memory impairment to severe physical and mental disability.
As expected, if brain damage persists, it negatively impacts patients’ quality of life.
Cognitive impairment could include limited attention span, personality disturbances, movement disorders ( i.e. Parkinsonism ), and even dementia; however, memory seems to be the cognitive function most affected in survivors of cardiac arrest.
Neuropsychological studies have shown deficits in different cognitive areas including memory ( 64.3% ), executive functioning ( 21.4% ), language ( 21.4% ), and perception ( 14.3% ).
In 1990, the Utstein style was developed in order to standardize the results of resuscitation studies; this includes neurological evaluation using either the Cerebral Performance Category ( CPC ) or the Modified Rankin Scale ( mRS ).
Cerebral Performance Category classifies patients on a scale from 1 to 5 ( 1 = good cerebral performance; 5 = deceased ) while the mRS classifies patients on a 0–6 scale ( 0 = asymptomatic; 6 = deceased ); CPC scores of 1–2 and mRS scores of 0–3 are considered favourable neurological outcomes.
These criteria are included as a reminder of the risk of neurological dysfunction among survivors of cardiac arrest.
Memory impairment after cardiac arrest
In patients successfully treated for an OHCA in a rapid emergency response program, the long-term survival and quality of life are similar to age- and gender-matched controls.
However, if cognitive assessment is evaluated in detail, memory loss is prevalent.
Alexander et al. reported that among 30 selected patients ( 1 day of coma, with responsiveness after 24 h but with remaining confusion for 7 days ), only one-third of the sample suffered from motor impairment after the event, but the total population showed at least a mild degree of memory impairment.
Torgersen et al.also reported that even after therapeutic hypothermia, 52% of the patients who suffered cardiac arrest showed cognitive impairment, especially episodic memory dysfunction.
This finding is not new, in 1996, Grubb et al. demonstrated in a population of 35 patients that up to 37% of the patients suffered chronic memory impairment after cardiac arrest, and that memory dysfunction was inversely proportional to the duration of the event.
Memory impairment after cardiac arrest does not seem to improve over time; a case-control study comparing OHCA patients with patients who suffered acute coronary syndrome without OHCA ( controls ) showed that memory impairment recorded at 3-month follow-up remained unchanged after 12 months, with just mild improvement of other functions.
Further, only 16% returned to work after the cardiac arrest whereas more than 94% of controls returned to work.
This study also evaluated quality of life among cardiac arrest survivors and controls; physical quality of life was not perceived as impaired in either group, however, the cases perceived a worse quality of life as a result of memory impairment.
Therapeutic hypothermia to prevent cognitive impairment after cardiac arrest
Although the effects of hypothermia have been evaluated in humans and experimental models before, in 1956 Marchand and Allan developed an experimental model to measure the effects of hypothermia on the heart and brain.
The first studies of therapeutic hypothermia in cardiac arrest patients were performed in the 1950s. Later, Zola-Morgan et al. reported that ischaemic episodes damaged CA1 hippocampal cells.
The benefits of induced hypothermia were demonstrated in animal models in the nineties.
At the present time, compelling evidence supports the use of targeted therapeutic hypothermia.
Effectiveness of therapeutic hypothermia to prevent cognitive impairment has been reported with varying results among different authors. For example, Fugate et al. followed 56 survivors of cardiac arrest treated with therapeutic hypothermia.
Twenty-month follow-up interviews yielded results favouring the use of this therapy: 33 ( 60% ) patients were reported as being cognitively normal, with 79% of working patients returning to their normal activities after the event.
In contrast, a randomized clinical trial ( RCT ) of 70 patients comparing therapeutic hypothermia to a normothermic control group ( without further intervention ), found no statistically significant difference in cognitive function between the two groups, although the authors suggests that differences in the neuropsychological tests employed ( previous prospective studies focusing on memory functions rather than executive functions ) might explain the neutral findings in this RCT.
Current guidelines for hospital care after cardiac arrest recommend the use of targeted therapeutic hypothermia between 32 and 34°C for 48 h.
After publication of these guidelines, a systematic review by Schenone et al.reported that mortality was halved [ odds ratio ( OR ) = 0.51, 95% CI 0.4–0.64 ] and neurological impairment caused by arrest-induced hypoxia was significantly lower ( good neurological outcome; OR = 2.48, 95% CI 1.91–3.22 ) in patients who underwent therapeutic hypothermia compared with those who did not. ( Xagena )
Source: Dagres N et al, Europace, 2018