Estimated cerebral oxyhemoglobin as a useful indicator of neuroprotection in patients with post-cardiac arrest syndrome: a prospective, multicenter observational study

Kei Hayashida, Kei Nishiyama, Masaru Suzuki, Takayuki Abe, Tomohiko Orita, Noritoshi Ito, Shingo Hori, Kei Hayashida, Kei Nishiyama, Masaru Suzuki, Takayuki Abe, Tomohiko Orita, Noritoshi Ito, Shingo Hori

Abstract

Introduction: Little is known about oxyhemoglobin (oxy-Hb) levels in the cerebral tissue during the development of anoxic and ischemic brain injury. We hypothesized that the estimated cerebral oxy-Hb level, a product of Hb and regional cerebral oxygen saturation (rSO2), determined at hospital arrival may reflect the level of neuroprotection in patients with post-cardiac arrest syndrome (PCAS).

Methods: The Japan Prediction of neurological Outcomes in patients with Post cardiac arrest (J-POP) registry is a prospective, multicenter, cohort study to test whether rSO2 predicts neurological outcomes after out-of-hospital cardiac arrest (OHCA). This study assessed a subgroup of consecutive patients who fulfilled the J-POP registry criteria and successfully achieved return of spontaneous circulation (ROSC) from OHCA. The primary outcome measure was the neurological status at 90 days.

Results: We analyzed data from 495 consecutive comatose survivors who were successfully resuscitated from OHCA, including 119 comatose patients with prehospital return of spontaneous circulation (ROSC; 24.0%) and 376 cardiac arrests at hospital arrival. In total, 75 patients (15.1%) presented with good neurological outcomes. Univariate analysis revealed that the cerebral oxy-Hb levels were significantly higher in patients with good outcomes. Multivariate logistic regression using the backward elimination method confirmed that the oxy-Hb level was a significant predictor of good neurological outcomes (adjusted odds ratio: 1.27, 95% confidence interval (CI): 1.11 to 1.46). Analysis of the area under the receiver operating characteristic curve (AUC) revealed that an oxy-Hb cut-off of 5.5 provided optimal sensitivity and specificity for predicting good neurological outcomes (AUC: 0.87, 95% CI: 0.83 to 0.91; sensitivity: 77.3%; specificity: 85.6%). The oxy-Hb level appeared to be an excellent prognostic indicator with significant advantages over rSO2 and base excess according to AUC analysis. The significant trend for good neurological outcomes was consistent, even in the subgroup of patients who achieved return of spontaneous circulation upon hospital arrival (1st quartile: 0%; 2nd quartile: 16.7%; 3rd quartile: 29.4%; 4th quartile: 53.3%, P <0.05).

Conclusions: The cerebral oxy-Hb level may predict neurological outcomes and is a simple and excellent indicator of neuroprotection in patients with PCAS.

Trial registration: UMIN Clinical Trials Registry UMIN000005065. Registered 1 April 2011.

Figures

Figure 1
Figure 1
Patient selection.
Figure 2
Figure 2
The relation between rSO2and hemoglobin during resuscitation at hospital arrival. Oxy-Hb, estimated oxy-hemoglobin; rSO2, regional cerebral oxygen saturation; ROSC, return of spontaneous circulation.
Figure 3
Figure 3
The relation between estimated oxyhemoglobin levels and arterial pH at hospital arrival. Hb, hemoglobin; Oxy-Hb, estimated oxy-hemoglobin; rSO2, regional cerebral oxygen saturation; *P < 0.01, **P < 0.001.
Figure 4
Figure 4
The relation between estimated oxy-Hb at hospital arrival and cerebral performance category. CPC, cerebral performance category; Oxy-Hb, oxyhemoglobin.
Figure 5
Figure 5
AUC of each potential indicator for predicting neurologic outcome at 90 days. The area under the receiver operating characteristic curve (AUC) of each potential indicator to predict good neurologic outcome at 90-day hospital admission in patients with post–cardiac arrest syndrome. *P < 0.001 versus AUC of oxyhemoglobin.
Figure 6
Figure 6
The association between rSO2and estimated cerebral oxy-hemoglobin and frequency of good neurologic outcomes. Study participants were divided into four groups by oxy-Hb and rSO2 quartiles (Q1, n = 126; Q2, n = 122; Q3, n = 124; Q4, n = 123 for oxy-Hb: Q1, n = 221; Q2, n = 28; Q3, n = 125; Q4, n = 121 for rSO2). (a) Subgroup of patients with sustained cardiac arrest at hospital arrival (n = 376). (b) Subgroup of patients with ROSC at hospital arrival (n = 119). Oxy-Hb, estimated oxyhemoglobin; rSO2, regional cerebral oxygen saturation; ROSC, return of spontaneous circulation.

References

    1. Booth CM, Boone RH, Tomlinson G, Detsky AS. Is this patient dead, vegetative, or severely neurologically impaired? Assessing outcome for comatose survivors of cardiac arrest. JAMA. 2004;291:870–879. doi: 10.1001/jama.291.7.870.
    1. Peberdy MA, Callaway CW, Neumar RW, Geocadin RG, Zimmerman JL, Donnino M, Gabrielli A, Silvers SM, Zaritsky AL, Merchant R, Vanden Hoek TL, Kronick SL. Part 9: post-cardiac arrest care, American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;2010:S768–S786. doi: 10.1161/CIRCULATIONAHA.110.971002.
    1. Becker LB, Aufderheide TP, Geocadin RG, Callaway CW, Lazar RM, Donnino MW, Nadkarni VM, Abella BS, Adrie C, Berg RA, Merchant RM, O’Connor RE, Meltzer DO, Holm MB, Longstreth WT, Halperin HR. Primary outcomes for resuscitation science studies: a consensus statement from the American Heart Association. Circulation. 2011;124:2158–2177. doi: 10.1161/CIR.0b013e3182340239.
    1. Cronberg T, Brizzi M, Liedholm LJ, Rosen I, Rubertsson S, Rylander C, Friberg H. Neurological prognostication after cardiac arrest: recommendations from the Swedish Resuscitation Council. Resuscitation. 2013;84:867–872. doi: 10.1016/j.resuscitation.2013.01.019.
    1. Peberdy MA, Kaye W, Ornato JP, Larkin GL, Nadkarni V, Mancini ME, Berg RA, Nichol G, Lane-Trultt T. Cardiopulmonary resuscitation of adults in the hospital: a report of 14720 cardiac arrests from the National Registry of Cardiopulmonary Resuscitation. Resuscitation. 2003;58:297–308. doi: 10.1016/S0300-9572(03)00215-6.
    1. Stiell IG, Wells GA, Field B, Spaite DW, Nesbitt LP, De Maio VJ, Nichol G, Cousineau D, Blackburn J, Munkley D, Luinstra-Toohey L, Campeau T, Dagnone E, Lyver M. Advanced cardiac life support in out-of-hospital cardiac arrest. N Engl J Med. 2004;351:647–656. doi: 10.1056/NEJMoa040325.
    1. Neumar RW, Otto CW, Link MS, Kronick SL, Shuster M, Callaway CW, Kudenchuk PJ, Ornato JP, McNally B, Silvers SM, Passman RS, White RD, Hess EP, Tang W, Davis D, Sinz E, Morrison LJ. Part 8: Adult advanced cardiovascular life support, American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;2010:S729–S767. doi: 10.1161/CIRCULATIONAHA.110.970988.
    1. Travers AH, Rea TD, Bobrow BJ, Edelson DP, Berg RA, Sayre MR, Berg MD, Chameides L, O’Connor RE, Swor RA. Part 4: CPR overview, American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;2010:S676–S684. doi: 10.1161/CIRCULATIONAHA.110.970913.
    1. Berg RA, Hemphill R, Abella BS, Aufderheide TP, Cave DM, Hazinski MF, Lerner EB, Rea TD, Sayre MR, Swor RA. Part 5: Adult basic life support, American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;2010:S685–S705. doi: 10.1161/CIRCULATIONAHA.110.970939.
    1. Ahn A, Nasir A, Malik H, D’Orazi F, Parnia S. A pilot study examining the role of regional cerebral oxygen saturation monitoring as a marker of return of spontaneous circulation in shockable (VF/VT) and non-shockable (PEA/Asystole) causes of cardiac arrest. Resuscitation. 2013;84:1713–1716. doi: 10.1016/j.resuscitation.2013.07.026.
    1. Ahn A, Yang J, Inigo-Santiago L, Parnia S. A feasibility study of cerebral oximetry monitoring during the post-resuscitation period in comatose patients following cardiac arrest. Resuscitation. 2014;85:522–526. doi: 10.1016/j.resuscitation.2013.12.007.
    1. Newman DH, Callaway CW, Greenwald IB, Freed J. Cerebral oximetry in out-of-hospital cardiac arrest: standard CPR rarely provides detectable hemoglobin-oxygen saturation to the frontal cortex. Resuscitation. 2004;63:189–194. doi: 10.1016/j.resuscitation.2004.05.003.
    1. Pellicer A. Bravo Mdel C: Near-infrared spectroscopy: a methodology-focused review. Semin Fetal Neonatal Med. 2011;16:42–49. doi: 10.1016/j.siny.2010.05.003.
    1. Orihashi K, Sueda T, Okada K, Imai K. Near-infrared spectroscopy for monitoring cerebral ischemia during selective cerebral perfusion. Eur J Cardiothorac Surg. 2004;26:907–911. doi: 10.1016/j.ejcts.2004.06.014.
    1. Morrison LJ, Deakin CD, Morley PT, Callaway CW, Kerber RE, Kronick SL, Lavonas EJ, Link MS, Neumar RW, Otto CW, Parr M, Shuster M, Sunde K, Peberdy MA, Tang W, Hoek TL, Bottiger BW, Drajer S, Lim SH, Nolan JP. Part 8: Advanced life support, International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Circulation. 2010;2010:S345–S421. doi: 10.1161/CIRCULATIONAHA.110.971051.
    1. Kitamura T, Iwami T, Kawamura T, Nagao K, Tanaka H, Hiraide A. Nationwide public-access defibrillation in Japan. N Engl J Med. 2010;362:994–1004. doi: 10.1056/NEJMoa0906644.
    1. Murkin JM, Adams SJ, Novick RJ, Quantz M, Bainbridge D, Iglesias I, Cleland A, Schaefer B, Irwin B, Fox S. Monitoring brain oxygen saturation during coronary bypass surgery: a randomized, prospective study. Anesth Analg. 2007;104:51–58. doi: 10.1213/01.ane.0000246814.29362.f4.
    1. Yao FS, Tseng CC, Ho CY, Levin SK, Illner P. Cerebral oxygen desaturation is associated with early postoperative neuropsychological dysfunction in patients undergoing cardiac surgery. J Cardiothorac Vasc Anesth. 2004;18:552–558. doi: 10.1053/j.jvca.2004.07.007.
    1. Sasson C, Rogers MA, Dahl J, Kellermann AL. Predictors of survival from out-of-hospital cardiac arrest: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2010;3:63–81. doi: 10.1161/CIRCOUTCOMES.109.889576.
    1. Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol. 1996;49:1373–1379. doi: 10.1016/S0895-4356(96)00236-3.
    1. DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44:837–845. doi: 10.2307/2531595.
    1. Ethical guidelines for epidemiologic research. 2008.
    1. SOS-KANTO study group Relationship between the hemoglobin level at hospital arrival and post-cardiac arrest neurologic outcome. Am J Emerg Med. 2012;30:770–774. doi: 10.1016/j.ajem.2011.03.031.
    1. Takasu A, Sakamoto T, Okada Y. Arterial base excess after CPR: the relationship to CPR duration and the characteristics related to outcome. Resuscitation. 2007;73:394–399. doi: 10.1016/j.resuscitation.2006.10.014.
    1. Ito N, Nishiyama K, Callaway CW, Orita T, Hayashida K, Arimoto H, Abe M, Endo T, Murai A, Ishikura K, Yamada N, Mizobuchi M, Anan H, Okuchi K, Yasuda H, Mochizuki T, Tsujimura Y, Nakayama T, Hatanaka T, Nagao K. Noninvasive regional cerebral oxygen saturation for neurological prognostication of patients with out-of-hospital cardiac arrest: a prospective multicenter observational study. Resuscitation. 2014;85:778–784. doi: 10.1016/j.resuscitation.2014.02.012.
    1. Kilgannon JH, Jones AE, Parrillo JE, Dellinger RP, Milcarek B, Hunter K, Shapiro NI, Trzeciak S. Relationship between supranormal oxygen tension and outcome after resuscitation from cardiac arrest. Circulation. 2011;123:2717–2722. doi: 10.1161/CIRCULATIONAHA.110.001016.
    1. Robertson CS, Gopinath SP, Chance B. A new application for near-infrared spectroscopy: detection of delayed intracranial hematomas after head injury. J Neurotrauma. 1995;12:591–600. doi: 10.1089/neu.1995.12.591.
    1. Toet MC, Flinterman A, Laar I, Vries JW, Bennink GB, Uiterwaal CS, Bel F. Cerebral oxygen saturation and electrical brain activity before, during, and up to 36 hours after arterial switch procedure in neonates without pre-existing brain damage: its relationship to neurodevelopmental outcome. Exp Brain Res. 2005;165:343–350. doi: 10.1007/s00221-005-2300-3.
    1. Billet N, Meex I, Vanderlaenen M, Heylen R, Boer W, Deyne C, Jans F. Cerebral oximetry and brain death in the ICU: data from seven cases. Crit Care. 2012;16:294. doi: 10.1186/cc10901.
    1. Blohm ME, Obrecht D, Hartwich J, Singer D. Effect of cerebral circulatory arrest on cerebral near-infrared spectroscopy in pediatric patients. Paediatr Anaesth. 2014;24:393–399. doi: 10.1111/pan.12328.
    1. Asim K, Gokhan E, Ozlem B, Ozcan Y, Deniz O, Kamil K, Murat Z, Aydin C, Selman Y. Near infrared spectrophotometry (cerebral oximetry) in predicting the return of spontaneous circulation in out-of-hospital cardiac arrest. Am J Emerg Med. 2014;32:14–17. doi: 10.1016/j.ajem.2013.09.010.
    1. The Hypothermia after Cardiac Arrest Study Group Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346:549–556. doi: 10.1056/NEJMoa012689.
    1. Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346:557–563. doi: 10.1056/NEJMoa003289.
    1. Mentzelopoulos SD, Malachias S, Chamos C, Konstantopoulos D, Ntaidou T, Papastylianou A, Kolliantzaki I, Theodoridi M, Ischaki H, Makris D, Zakynthinos E, Zintzaras E, Sourlas S, Aloizos S, Zakynthinos SG. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial. JAMA. 2013;310:270–279. doi: 10.1001/jama.2013.7832.
    1. Oddo M, Rossetti AO. Predicting neurological outcome after cardiac arrest. Curr Opin Crit Care. 2011;17:254–259. doi: 10.1097/MCC.0b013e328344f2ae.
    1. Levy DE, Bates D, Caronna JJ, Cartlidge NE, Knill-Jones RP, Lapinski RH, Singer BH, Shaw DA, Plum F. Prognosis in nontraumatic coma. Ann Intern Med. 1981;94:293–301. doi: 10.7326/0003-4819-94-3-293.
    1. Wijdicks EF, Hijdra A, Young GB, Bassetti CL, Wiebe S. Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006;67:203–210. doi: 10.1212/.
    1. Rossetti AO, Oddo M, Logroscino G, Kaplan PW. Prognostication after cardiac arrest and hypothermia: a prospective study. Ann Neurol. 2010;67:301–307.
    1. Zandbergen EG, Hijdra A, Koelman JH, Hart AA, Vos PE, Verbeek MM, de Haan RJ. Prediction of poor outcome within the first 3 days of postanoxic coma. Neurology. 2006;66:62–68. doi: 10.1212/01.wnl.0000191308.22233.88.
    1. Bouwes A, Binnekade JM, Zandstra DF, Koelman JH, van Schaik IN, Hijdra A, Horn J. Somatosensory evoked potentials during mild hypothermia after cardiopulmonary resuscitation. Neurology. 2009;73:1457–1461. doi: 10.1212/WNL.0b013e3181bf98f4.
    1. Grubb NR, Simpson C, Sherwood RA, Abraha HD, Cobbe SM, O’Carroll RE, Deary I, Fox KA. Prediction of cognitive dysfunction after resuscitation from out-of-hospital cardiac arrest using serum neuron-specific enolase and protein S-100. Heart. 2007;93:1268–1273. doi: 10.1136/hrt.2006.091314.
    1. Rundgren M, Karlsson T, Nielsen N, Cronberg T, Johnsson P, Friberg H. Neuron specific enolase and S-100B as predictors of outcome after cardiac arrest and induced hypothermia. Resuscitation. 2009;80:784–789. doi: 10.1016/j.resuscitation.2009.03.025.
    1. Wijman CA, Mlynash M, Caulfield AF, Hsia AW, Eyngorn I, Bammer R, Fischbein N, Albers GW, Moseley M. Prognostic value of brain diffusion-weighted imaging after cardiac arrest. Ann Neurol. 2009;65:394–402. doi: 10.1002/ana.21632.
    1. Wu O, Sorensen AG, Benner T, Singhal AB, Furie KL, Greer DM. Comatose patients with cardiac arrest: predicting clinical outcome with diffusion-weighted MR imaging. Radiology. 2009;252:173–181. doi: 10.1148/radiol.2521081232.
    1. Choi SP, Park KN, Park HK, Kim JY, Youn CS, Ahn KJ, Yim HW. Diffusion-weighted magnetic resonance imaging for predicting the clinical outcome of comatose survivors after cardiac arrest: a cohort study. Crit Care. 2010;14:R17. doi: 10.1186/cc8874.
    1. Adrie C, Cariou A, Mourvillier B, Laurent I, Dabbane H, Hantala F, Rhaoui A, Thuong M, Monchi M. Predicting survival with good neurological recovery at hospital admission after successful resuscitation of out-of-hospital cardiac arrest: the OHCA score. Eur Heart J. 2006;27:2840–2845. doi: 10.1093/eurheartj/ehl335.
    1. Howell MD, Donnino MW, Talmor D, Clardy P, Ngo L, Shapiro NI. Performance of severity of illness scoring systems in emergency department patients with infection. Acad Emerg Med. 2007;14:709–714. doi: 10.1111/j.1553-2712.2007.tb01866.x.
    1. Olsson T, Terent A, Lind L. Rapid Emergency Medicine score: a new prognostic tool for in-hospital mortality in nonsurgical emergency department patients. J Intern Med. 2004;255:579–587. doi: 10.1111/j.1365-2796.2004.01321.x.
    1. Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Aneman A, Al-Subaie N, Boesgaard S, Bro-Jeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Kober L, Langorgen J, Lilja G, Moller JE, Rundgren M, Rylander C, Smid O, Werer C, Winkel P, Friberg H. Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest. N Engl J Med. 2013;369:2197–2206. doi: 10.1056/NEJMoa1310519.
    1. Rittenberger JC, Callaway CW. Temperature management and modern post-cardiac arrest care. N Engl J Med. 2013;369:2262–2263. doi: 10.1056/NEJMe1312700.
    1. Madsen PL, Skak C, Rasmussen A, Secher NH. Interference of cerebral near-infrared oximetry in patients with icterus. Anesth Analg. 2000;90:489–493.
    1. Song JG, Jeong SM, Shin WJ, Jun IG, Shin K, Huh IY, Kim YK, Hwang GS. Laboratory variables associated with low near-infrared cerebral oxygen saturation in icteric patients before liver transplantation surgery. Anesth Analg. 2011;112:1347–1352. doi: 10.1213/ANE.0b013e318214b2b0.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner