Brain monitoring after cardiac arrest

INTRODUCTION

About two-thirds of patients admitted to an ICU after resuscitation from cardiac arrest die because of hypoxic–ischemic brain injury (HIBI) [1▪]. Limiting brain injury is a primary goal of postresuscitation care [2▪▪] and to this aim, neuromonitoring is paramount. Several neuromonitoring tools are currently available in patients with HIBI (Fig. 1). 

F1FIGURE 1:

Overview of the major neuromonitoring tools after cardiac arrest. A schematic presentation of means of monitoring the brain in patients treated in the intensive care unit after cardiac arrest. EEG, electroencephalogram; ICP, intracranial pressure; NIRS, near-infrared spectroscopy; PbtO2, brain tissue oxygen pressure; TCD, transcranial Doppler.

FB1Box 1:

no caption available

MONITORING ELECTRICAL CEREBRAL ACTIVITY

The electroencephalogram (EEG) is widely used for neuromonitoring in HIBI [3▪▪]. However, its signal is complex and includes a variety of abnormal patterns [4▪]. These have been codified by the American Clinical Neurophysiology Society (ACNS) in standard terminology for use in intensive care [5▪▪]. Immediately after the return of spontaneous circulation (ROSC), the amplitude of EEG is often markedly depressed or discontinuous. Suppression (EEG amplitude below 10 μV) or burst-suppression (suppression for more than half of the recording, alternating with electrical bursts) [5▪▪] are markers of severe HIBI and, especially if they appear after 24 h from ROSC, are almost invariably associated with poor long-term disability or death [6]. However, in patients who achieve neurological recovery, the EEG shows progressive background improvement towards continuous and normal-amplitude tracing [7▪].

The postarrest EEG background can also show superimposed epileptiform discharges. When isolated, discharges are of little significance in patients with HIBI. However, if discharges are abundant and/or appear repetitively in a regular fashion, they are called rhythmic or periodic patterns (RPPs) and deserve special attention. Seizures are RPPs lasting 10 s or more and having a frequency above 2.5 Hz or a spatiotemporal evolution [5▪▪]. Seizures or RPPs occur in about 30% of unconscious resuscitated patients. Still, because of sedation and/or muscular paralysis, these abnormalities often lack clinical manifestations and are only detectable on EEG. Seizures on EEG within 24–48 h from ROSC indicate severe HIBI and predict poor outcome. Conversely, later-appearing seizures do not exclude recovery [8].

EEG monitoring is commonly used to guide treatment with antiepileptic drugs (AEDs) after cardiac arrest. However, the benefits of AEDs in postarrest seizures remain unclear. In the multicenter randomized open-label TELSTAR trial on 172 unconscious postcardiac arrest patients with RPPs, a stepwise treatment including AEDs, hypnotics and barbiturates did not improve the rates of good neurological survival at 6 months compared with no treatment [9▪▪]. However, a subgroup analysis showed a nonsignificant trend towards improvement with AEDs in patients with seizures as opposed to those with slower RPPs.

Full-montage routine EEG for 20–30 min is most commonly used after HIBI [10] and is available during office hours at most hospitals. Continuous EEG monitoring facilitates assessment of the EEG evolution after ROSC and increases sensitivity for seizure detection compared with routine EEG [11], but there is no evidence that it improves outcome prediction compared with intermittent EEG [12].

MONITORING ARTERIAL CEREBRAL BLOOD FLOW

Experimental evidence shows that after an initial transient post-ROSC hyperemia, cerebral blood flow (CBF) decreases significantly [13] in patients with HIBI. Although CBF cannot be directly assessed at the bedside, transcranial Doppler sonography (TCD) provides a noninvasive estimate of CBF velocities (CBFV). Changes in CBFV on TCD mirror changes in CBF if the arterial diameter remains unchanged. In two early studies [14,15], mean CBFV in the middle cerebral artery (MCA) decreased immediately after ROSC but returned to normal within 72 h with no difference between survivors and nonsurvivors. However, while in survivors, the cerebral oxygen extraction fraction (CEO2) decreased slightly and returned towards normal values within 72 h, in nonsurvivors, the CEO2 showed a significant decrease and remained low at 72 h. In line with these results, a recent study [16] showed supranormal levels (>75%) of jugular venous oxygen saturation in HIBI patients with poor neurological outcome and elevated brain injury biomarkers. Overall, these findings suggest that, following cardiac arrest, a reduction in CBF occurs, paralleled by a reduction in cerebral metabolism, which is more pronounced in patients with more severe HIBI. The GOODYEAR trial (NCT04000334) is investigating the feasibility of an early-goal-directed hemodynamic management guided by TCD during the first 12 h after ROSC.

MONITORING INTRACRANIAL PRESSURE

HIBI is often associated with neuronal swelling (cytotoxic edema) and severe neuroinflammation with disruption of the blood–brain barrier (BBB), leading to vasogenic edema. These may result in both increased intracranial pressure (ICP) [17] [i.e. intracranial hypertension (ICHT)] and reduced cerebral perfusion pressure (CPP). In one study on 84 comatose postcardiac arrest patients, more than one quarter experienced ICHT (ICP >25 mmHg) by their second day after ROSC and in more than half of them CPP dropped below 50 mmHg [18]. In a physiologic study (n = 10), ICP was monitored via an intraparenchymal probe at a median of 8.5 h after ROSC and for a median duration of 40.5 h (interquartile range 24–51 h). Although the mean ICP was only 14 mmHg, ICHT (ICP >20 mmHg) occurred during 22% of the total neuromonitoring time. Two patients developed a lethal refractory ICHT despite maximal medical therapy. In addition, all patients exhibited decreased intracranial compliance, measured in real time as the correlation coefficient between the mean ICP and mean pulse amplitude pressure of the ICP waveform [19]. In another physiologic study (n = 10), ICP and lactate/pyruvate ratio (LPR) were measured hourly during the first 72 h after ROSC via an intraparenchymal catheter and a cerebral microdialysis membrane in 10 patients undergoing therapeutic hypothermia followed by gradual rewarming for 24–48 h. In patients with poor neurological outcome, ICP was consistently higher and further increased during rewarming. LPR was normal during hypothermia but increased significantly after rewarming in patients with poor neurological outcome, suggesting anaerobic cerebral metabolism [20].

Invasive ICP monitoring is not routinely used in resuscitated patients because of the limited clinical experience and the concomitant use of antiplatelet and/or anticoagulant therapy. TCD may provide an alternative noninvasive estimate of ICHT based on the measurement of increased arterial vascular resistance from cerebral edema [21]. On TCD, vascular resistance is measured using pulsatility index, which is calculated as (systolic – diastolic CBFV)/mean CBFV. Pulsatility index values at least 1.20 indicate increased arterial resistance and suggest ICHT in this clinical scenario. In one study on 11 patients with HIBI, noninvasive ICP measured using pulsatility index showed a linear correlation (R = 0.30) with invasive ICP measured using an intraparenchymal probe and a good predictive value for ICHT [area under the receiver-operating characteristics (AUROC) curve = 0.91 (95% CI 0.83–1.00)] [22]. In a recent study (n = 42), while mean CBFV values at 6 h after ROSC were within normal range in most patients, pulsatility index was significantly increased (1.49 vs. 1.12, P = 0.01) in patients with poor neurological outcome, of whom six died of brain death [23].

The rationale for monitoring ICP after cardiac arrest is to treat ICHT from brain edema potentially exacerbating HIBI. There is still uncertainty on what is the best strategy for treating ICHT following cardiac arrest. Although hyperosmolar therapies mitigate cytotoxic brain edema, they may aggravate vasogenic edema [1▪,24] because of extravascular accumulation of osmotically active particles. Nevertheless, evidence of benefit from osmotherapy has been reported in brain edema following experimental cardiac arrest [25]. Moreover, a retrospective, single-center, matched observational cohort study (n = 65) showed that aggressive treatment of ICHT guided by neuromonitoring in patients with HIBI was associated with significantly higher rates of favorable neurological outcome vs. standard care [26▪]. To date, no clinical trial aimed at treating ICHT or mitigating brain edema in HIBI has been published.

MONITORING BRAIN OXYGENATION Brain tissue oxygen pressure

Although studies on TCD and jugular venous bulb oxygen saturation suggest a possible normal coupling between cerebral blood flow and metabolism in patients with HIBI [13–15], they did not directly assess the oxygenation level of the brain tissue. This is achieved by measuring PbtO2 at the interstitial level using an intraparenchymal probe. Brain oxygenation depends not only on oxygen delivery (i.e. cerebral blood flow and arterial oxygen content) but also on microcirculatory oxygen diffusion and cerebral metabolism [27]. A PbtO2 less than 20 mmHg is considered as the threshold to identify tissue hypoxia and trigger-specific interventions.

Occurrence of brain tissue hypoxia is a potential mechanism of reperfusion injury in HIBI. A study on 18 HIBI patients showed that low PbtO2 was associated with active release of brain injury biomarkers and cerebral release of interleukin-6, the latter suggesting a significant role for neuroinflammation in HIBI [28]. In another study (n = 10) from the same group, patients experienced a PbtO2 less than 20 mmHg for 38% of the monitoring time (743/1944 10 min averaged periods) [29]. The authors described two pathophysiologic phenotypes in this cohort. The first was a ‘diffusion-limited’ phenotype with persistent tissue hypoxia despite optimizing oxygen delivery, probably because of BBB disruption with resultant perivascular edema or mitochondrial dysfunction; the second was a ‘perfusion dependent’ phenotype, with intact oxygen diffusion [30]. Therapies aimed at mitigating brain tissue hypoxia, such as osmotic therapy or MAP augmentation, would be more likely effective in this latter phenotype.

Near-infrared spectroscopy

Near-infrared spectroscopy (NIRS) is a noninvasive tool to monitor the regional cerebral oxygenation (rSO2) using infrared light absorbance to calculate oxyhemoglobin and de-oxyhemoglobin [31]. In commercially available NIRS monitors, near infrared light is emitted from one diode and received by two diodes, all placed on the scalp above the frontal cortex [32]. The NIRS sampling volume is located about 2 cm underneath the skull. Since about 70% of the sampled blood is venous, normal rSO2 is approximately 60–80%.

Several observational studies have investigated NIRS for assessing the severity of HIBI, with conflicting results. In 2012, a multicenter study in Japan enrolling 596 patients who were unconscious after resuscitation from out-of-hospital cardiac arrest showed that rSO2 measured at hospital admission predicted 30-day neurological outcome more accurately than lactate (AUROC 0.91 vs. 0.77; P = 0.0001). However, subsequent studies did not confirm these findings [33–35]. A major problem with NIRS is contamination from extracerebral circulation [36]. In addition, NIRS is derived using proprietary algorithms that make it difficult to compare results obtained by different monitors [32]. At present, NIRS is not recommended for prognostication after cardiac arrest [2▪▪]. Like for other monitoring tools, rSO2 trends are probably more informative than absolute values.

Monitoring cerebral autoregulation

Normally, cerebral circulation maintains a stable CBF within a range of mean arterial pressure (MAP). This property is called cerebral autoregulation. However, in about one-third of patients with HIBI, the autoregulation plateau is narrowed and right-shifted [37]. Consequently, arterial hypotension after cardiac arrest may result in cerebral hypoperfusion, worsening HIBI. A pilot trial [38] and a larger clinical trial [39] showed that targeting high vs. low MAP after cardiac arrest does not change neurological outcome or the severity of HIBI measured with blood biomarkers. Alternatively, authors have advocated for individualized blood pressure targets aimed at maintaining MAP within the individual patient's range of intact autoregulation to optimize cerebral perfusion. To that aim, two derived parameters, cerebral oxygenation index (COx) and pressure reactivity index (PRx), have been investigated. These are the correlation coefficients between rSO2 and ICP, respectively, and MAP. An increase in COx or PRx with MAP suggests dysfunctional autoregulation, whereas a near zero or negative value of COx or PRx suggests that autoregulation is maintained. On the basis of that model, the ‘optimal MAP’ is the range corresponding to the lowest values of COx or PRx.

In one observational pilot study [40], 18 of 51 postcardiac arrest comatose patients had dysfunctional autoregulation measured using COx, and the time spent below the optimal MAP was associated with a lower likelihood of survival [odds ratio (OR) 0.97 (0.96–0.99), P = 0.02]. In another pilot study (n = 23), a higher COx during days 1–3 after cardiac arrest was independently associated with mortality at 3 months [41]. A similar association between dysfunctional autoregulation and poor outcome in patients with HIBI has also been found using PRx [42,43]. Recently, cerebral autoregulation in normothermia and hypothermia after cardiac arrest has been assessed using TCD. In a study on 50 patients resuscitated from out-of-hospital cardiac arrest, Crippa et al. investigated cerebral autoregulation during therapeutic hypothermia and after rewarming by measuring mean flow index (Mxa), which is the Pearson correlation coefficient between mean CBFV in the MCA and arterial blood pressure. Mxa above 0.3 defined altered cerebral autoregulation. Although the rates of altered autoregulation were similar between outcome groups during hypothermia, Mxa greater than 0.3 was significantly more common in patients who died or had poor neurological outcome after rewarming [31/36 (86%) vs. 7/14 (50%); P = 0.02]. On multivariate analysis, high Mxa was associated with poor neurological outcome [44].

Although dysfunctional cerebral autoregulation measured by COx or PRx is associated with poor neurological outcome after cardiac arrest, it is not clear if this simply represents a marker of HIBI severity or a therapeutic target, and no controlled trials assessing if an autoregulation-targeted MAP mitigates HIBI severity have been published to date.

Biomarkers

Biomarkers of brain injury are cellular components released by the brain tissue in response to an insult. The rationale for their use for assessing HIBI is that their release is proportional to the severity of the cellular injury. The most studied biomarkers are neuron-specific enolase (NSE), S-100B, neurofilament light chain (NfL), Tau, GFAP and UCH-1. Of these, only NSE is widely used in clinical practice, and is the only recommended in postresuscitation care guidelines [2▪▪]. NSE, like UCH, originates from the neuronal body, while NfL and Tau are released from the axons, and S100B, GFAP from the glial cells [45].

Understanding the kinetics of biomarkers is important for their correct clinical use. NSE blood levels peak at 48–72 h after ROSC, when their accuracy for assessing HIBI severity is maximal [6,45]. NSE half-life is 24–30 h, so that significantly high levels of NSE can still be found at 4-5 days after ROSC and beyond in poor outcome patients [46,47]. Although NSE levels increase from 24 to 72 h in patients with severe HIBI, they decrease or remain stable in patients who recover. In one study, a 1.7 ratio between NSE values at 48 h and those at 24 h after ROSC, and a 1.3 ratio between values at 72 and 24 h was 100% specific for poor neurological outcome [48]. Similar results have been found in other studies [49,50]. The European Resuscitation Council and European Society of Intensive Care (ERC-ESICM) guidelines for postresuscitation care suggest measuring NSE serially between 24 and 72 h after ROSC [2▪▪] and recommend using a NSE threshold of 60 μg/l at 48–72 h for prediction of poor outcome in HIBI.

Among recently investigated biomarkers of HIBI, NfL is the most promising. In multicenter biobank studies [51,52] NfL was more accurate than NSE for predicting poor neurological outcome, and its accuracy was high as early as 24 h after ROSC [AUROC 0.94 (0.92–0.95)]. The major limitation of NfL is that, because of its limited diffusion through the blood–brain barrier, its plasmatic levels are very low and require specific ultrasensitive assays [53]. Moreover, the NfL cut-off levels for identifying irreversible HIBI vary widely across studies, and its optimal threshold has not yet been identified.

CONCLUSION

Cardiac arrest causes an extensive brain injury of variable degree whose outcomes vary from complete recovery to severe disability or death. After the initial ischemia, reperfusion injury evolves over time and may result in neuronal membrane instability, brain edema, intracranial hypertension, brain hypoperfusion and reduced autoregulation. All these changes present an indication for neuromonitoring after cardiac arrest. Among the available tools, EEG is useful for prognostication and for seizure detection and treatment. ICP, TCD, PbtO2 and NIRS may guide clinicians for optimizing CBF and brain oxygenation and perfusion. Serial assessment of biomarkers is useful for assessing the severity of brain injury and predict the likelihood of recovery from postanoxic coma. In addition to their potential clinical applications, all these neuromonitoring tools are undergoing active research aimed at increasing our understanding of the pathophysiology and optimal management of HIBI.

Acknowledgements

None.

Financial support and sponsorship

None.

Conflicts of interest

C.S. is co-author of articles mentioned in this review. M.B.S. reports lecture fees and travel grants from BARD Medical. He is also co-author of articles mentioned in this review. F.S.T. is Scientific Advisor for Neuroptics and Nihon Khoden. He is also co-author of articles mentioned in this review.

REFERENCES AND RECOMMENDED READING

Papers of particular interest, published within the annual period of review, have been highlighted as:

▪ of special interest

▪▪ of outstanding interest

REFERENCES 1▪. Sandroni C, Cronberg T, Sekhon M. Brain injury after cardiac arrest: pathophysiology, treatment, and prognosis. Intensive Care Med 2021; 47:1393–1414. 2▪▪. Nolan JP, Sandroni C, Bottiger BW, et al. European Resuscitation Council and European Society of Intensive Care Medicine guidelines 2021: postresuscitation care. Intensive Care Med 2021; 47:369–421. 3▪▪. Alkhachroum A, Appavu B, Egawa S, et al. Electroencephalogram in the intensive care unit: a focused look at acute brain injury. Intensive Care Med 2022; 48:1443–1462. 4▪. Sandroni C, Cronberg T, Hofmeijer J. EEG monitoring after cardiac arrest. Intensive Care Med 2022; 48:1439–1442. 5▪▪. Hirsch LJ, Fong MWK, Leitinger M, et al. American Clinical Neurophysiology Society's Standardized Critical Care EEG terminology: 2021 version. J Clin Neurophysiol 2021; 38:1–29. 6. Sandroni C, D’Arrigo S, Cacciola S, et al. Prediction of poor neurological outcome in comatose survivors of cardiac arrest: a systematic review. Intensive Care Med 2020; 46:1803–1851. 7▪. Sandroni C, D’Arrigo S, Cacciola S, et al. Prediction of good neurological outcome in comatose survivors of cardiac arrest: a systematic review. Intensive Care Med 2022; 48:389–413. 8. Westhall E, Rosen I, Rundgren M, et al. Time to epileptiform activity and EEG background recovery are independent predictors after cardiac arrest. Clin Neurophysiol 2018; 129:1660–1668. 9▪▪. Ruijter BJ, Keijzer HM, Tjepkema-Cloostermans MC, et al. Treating rhythmic and periodic EEG patterns in comatose survivors of cardiac arrest. N Engl J Med 2022; 386:724–734. 10. Friberg H, Cronberg T, Dunser MW, et al. Survey on current practices for neurological prognostication after cardiac arrest. Resuscitation 2015; 90:158–162. 11. Elmer J, Coppler PJ, Solanki P, et al. Sensitivity of continuous electroencephalography to detect ictal activity after cardiac arrest. JAMA Netw Open 2020; 3:e203751. 12. Urbano V, Alvarez V, Schindler K, et al. Continuous versus routine EEG in patients after cardiac arrest: analysis of a randomized controlled trial (CERTA). Resuscitation 2022; 176:68–73. 13. Buunk G, van der Hoeven JG, Meinders AE. Cerebral blood flow after cardiac arrest. Netherlands J Med 2000; 57:106–112. 14. Hoedemaekers CW, Ainslie PN, Hinssen S, et al. Low cerebral blood flow after cardiac arrest is not associated with anaerobic cerebral metabolism. Resuscitation 2017; 120:45–50. 15. Lemiale V, Huet O, Vigué B, et al. Changes in cerebral blood flow and oxygen extraction during postresuscitation syndrome. Resuscitation 2008; 76:17–24. 16. Richter J, Sklienka P, Chatterjee N, et al. Elevated jugular venous oxygen saturation after cardiac arrest. Resuscitation 2021; 169:214–219. 17. Kang C, Jeong W, Park JS, et al. Different stratification of physiological factors affecting cerebral perfusion pressure in hypoxic-ischemic brain injury after cardiac arrest according to visible or non-visible primary brain injury: a retrospective observational study. J Clin Med 2021; 10: 18. Gueugniaud PY, Garcia-Darennes F, Gaussorgues P, et al. Prognostic significance of early intracranial and cerebral perfusion pressures in postcardiac arrest anoxic coma. Intensive Care Med 1991; 17:392–398. 19. Sekhon MS, Griesdale DE, Ainslie PN, et al. Intracranial pressure and compliance in hypoxic ischemic brain injury patients after cardiac arrest. Resuscitation 2019; 141:96–103. 20. Hifumi T, Kawakita K, Yoda T, et al. Association of brain metabolites with blood lactate and glucose levels with respect to neurological outcomes after out-of-hospital cardiac arrest: a preliminary microdialysis study. Resuscitation 2017; 110:26–31. 21. Rasulo FA, Bertuetti R, Robba C, et al. The accuracy of transcranial Doppler in excluding intracranial hypertension following acute brain injury: a multicenter prospective pilot study. Crit Care 2017; 21:44. 22. Cardim D, Griesdale DE, Ainslie PN, et al. A comparison of noninvasive versus invasive measures of intracranial pressure in hypoxic ischaemic brain injury after cardiac arrest. Resuscitation 2019; 137:221–228. 23. Rafi S, Tadie JM, Gacouin A, et al. Doppler sonography of cerebral blood flow for early prognostication after out-of-hospital cardiac arrest: DOTAC study. Resuscitation 2019; 141:188–194. 24. Hayman EG, Patel AP, Kimberly WT, et al. Cerebral edema after cardiopulmonary resuscitation: a therapeutic target following cardiac arrest? Neurocrit Care 2018; 28:276–287. 25. Nakayama S, Migliati E, Amiry-Moghaddam M, et al. Osmotherapy with hypertonic saline attenuates global cerebral edema following experimental cardiac arrest via perivascular pool of aquaporin-4. Crit Care Med 2016; 44:e702–e710. 26▪. 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; [in press]. 27. Robba C, Taccone FS, Citerio G. Monitoring cerebral oxygenation in acute brain-injured patients. Intensive Care Med 2022; 48:1463–1466. 28. Hoiland RL, Ainslie PN, Wellington CL, et al. Brain hypoxia is associated with neuroglial injury in humans post-cardiac arrest. Circ Res 2021; 129:583–597. 29. Sekhon MS, Gooderham P, Menon DK, et al. The burden of brain hypoxia and optimal mean arterial pressure in patients with hypoxic ischemic brain injury after cardiac arrest. Crit Care Med 2019; 47:960–969. 30. Hoiland RL, Robba C, Menon DK, Sekhon MS. Differential pathophysiologic phenotypes of hypoxic ischemic brain injury: considerations for postcardiac arrest trials. Intensive Care Med 2020; 46:1969–1971. 31. Sandroni C, Parnia S, Nolan JP. Cerebral oximetry in cardiac arrest: a potential role but with limitations. Intensive Care Med 2019; 45:904–906. 32. Skrifvars MB, Sekhon M, Åneman EA. Monitoring and modifying brain oxygenation in patients at risk of hypoxic ischaemic brain injury after cardiac arrest. Crit Care 2021; 25:312. 33. Genbrugge C, Eertmans W, Meex I, et al. What is the value of regional cerebral saturation in postcardiac arrest patients? A prospective observational study. Crit Care 2016; 20:327. 34. Storm C, Leithner C, Krannich A, et al. Regional cerebral oxygen saturation after cardiac arrest in 60 patients--a prospective outcome study. Resuscitation 2014; 85:1037–1041. 35. Jakkula P, Hästbacka J, Reinikainen M, et al. Near-infrared spectroscopy after out-of-hospital cardiac arrest. Crit Care 2019; 23:171. 36. Caccioppola A, Carbonara M, Macrì M, et al. Ultrasound-tagged near-infrared spectroscopy does not disclose absent cerebral circulation in brain-dead adults. Br J Anaesth 2018; 121:588–594. 37. Sundgreen C, Larsen FS, Herzog TM, et al. Autoregulation of cerebral blood flow in patients resuscitated from cardiac arrest. Stroke 2001; 32:128–132. 38. Jakkula P, Pettila V, Skrifvars MB, et al. Targeting low-normal or high-normal mean arterial pressure after cardiac arrest and resuscitation: a randomised pilot trial. Intensive Care Med 2018; 44:2091–2101. 39. Kjaergaard J, Møller JE, Schmidt H, et al. Blood-pressure targets in comatose survivors of cardiac arrest. N Engl J Med 2022; 387:1456–1466. 40. Ameloot K, Genbrugge C, Meex I, et al. An observational near-infrared spectroscopy study on cerebral autoregulation in postcardiac arrest patients: time to drop ’one-size-fits-all’ hemodynamic targets? Resuscitation 2015; 90:121–126. 41. Pham P, Bindra J, Chuan A, et al. Are changes in cerebrovascular autoregulation following cardiac arrest associated with neurological outcome? Results of a pilot study. Resuscitation 2015; 96:192–198. 42. Kirschen MP, Majmudar T, Diaz-Arrastia R, et al. Deviations from PRx-derived optimal blood pressure are associated with mortality after cardiac arrest. Resuscitation 2022; 175:81–87. 43. Balu R, Rajagopalan S, Baghshomali S, et al. Cerebrovascular pressure reactivity and intracranial pressure are associated with neurologic outcome after hypoxic-ischemic brain injury. Resuscitation 2021; 164:114–121. 44. Crippa IA, Vincent JL, Zama Cavicchi F, et al. Cerebral autoregulation in anoxic brain injury patients treated with targeted temperature management. J Intensive Care 2021; 9:67. 45. Gul SS, Huesgen KW, Wang KK, et al. Prognostic utility of neuroinjury biomarkers in post out-of-hospital cardiac arrest (OHCA) patient management. Medical Hypoth 2017; 105:34–47. 46. Nakstad ER, Staer-Jensen H, Wimmer H, et al. Late awakening, prognostic factors and long-term outcome in out-of-hospital cardiac arrest - results of the prospective Norwegian Cardio-Respiratory Arrest Study (NORCAST). Resuscitation 2020; 149:170–179. 47. Pfeifer R, Franz M, Figulla HR. Hypothermia after cardiac arrest does not affect serum levels of neuron-specific enolase and protein S-100b. Acta Anaesthesiol Scand 2014; 58:1093–1100. 48. Chung-Esaki HM, Mui G, Mlynash M, et al. The neuron specific enolase (NSE) ratio offers benefits over absolute value thresholds in postcardiac arrest coma prognosis. J Clin Neurosci 2018; 57:99–104. 49. Stammet P, Collignon O, Hassager C, et al. Neuron-specific enolase as a predictor of death or poor neurological outcome after out-of-hospital cardiac arrest and targeted temperature management at 33 degrees C and 36 degrees C. J Am Coll Cardiol 2015; 65:2104–2114. 50. Vondrakova D, Ostadal P, Kruger A, et al. Neuron-specific enolase is a strong predictor of neurological outcomes in cardiac arrest survivors treated with endovascular hypothermia. Resuscitation 2014; 85:S104. 51. Moseby-Knappe M, Mattsson N, Nielsen N, et al. Serum neurofilament light chain for prognosis of outcome after cardiac arrest. JAMA Neurol 2019; 76:64–71. 52. Wihersaari L, Ashton NJ, Reinikainen M, et al. Neurofilament light as an outcome predictor after cardiac arrest: a post hoc analysis of the COMACARE trial. Intensive Care Med 2021; 47:39–48. 53. Yuan A, Nixon RA. Neurofilament proteins as biomarkers to monitor neurological diseases and the efficacy of therapies. Front Neurosci 2021; 15:689938.

留言 (0)

沒有登入
gif