Journal of Emergencies, Trauma, and Shock
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CLINICAL INVESTIGATION  
Year : 2012  |  Volume : 5  |  Issue : 4  |  Page : 338-341
Significance of the carboxyhemoglobin level for out-of-hospital cardiopulmonary arrest


Department of Traumatology and Critical Care Medicine, National Defense Medical College, 3-2 Namiki Tokorozawa, Japan

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Date of Submission25-Jan-2011
Date of Acceptance30-Oct-2011
Date of Web Publication15-Oct-2012
 

   Abstract 

Background: At low concentrations, carbon monoxide (CO) can confer cyto and tissue-protective effects, such as endogenous Heme oxygenase 1 expression, which has antioxidative, anti-inflammatory, antiproliferative, and antiapoptotic effects. The level of carboxyhemoglobin in the blood is an indicator of the endogenous production of CO and inhaled CO. Aim of study: To investigate the significance of the value of carboxyhemoglobin for out-of-hospital (OH) cardiopulmonary arrest (CPA). Materials and Methods: This study involved a medical chart review of cases treated from January to December 2005. The inclusion criteria included a patient who was transported to this department due to an OH CPA. The exclusion criteria included a patient who did not undergo blood gas analysis on arrival and who experienced CPA due to acute carbon monoxide intoxication. The subjects were divided into two groups based on their final outcome of either survival or non-survival. Results: There was no significant difference associated with the sex, age, frequency of witness collapse, bystander cardiopulmonary arrest, electrocardiogram at scene, cause of CPA, value of PCO 2 , HCO3 - , and methemoglobin. The frequency of OH return of spontaneous circulation and the value of pH, PO 2 , base excess, and carboxyhemoglobin in the survival group were greater than those values in the non-survival group. There were no subjects whose carboxyhemoglobin level was 0% on arrival in the survival groups. Conclusion: There appeared to be an association between higher carboxyhemoglobin levels and survival in comparison with non-survival patients.

Keywords: Carbon monoxide, carboxyhemoglobin, cardiopulmonary arrest, outcome

How to cite this article:
Yanagawa Y. Significance of the carboxyhemoglobin level for out-of-hospital cardiopulmonary arrest. J Emerg Trauma Shock 2012;5:338-41

How to cite this URL:
Yanagawa Y. Significance of the carboxyhemoglobin level for out-of-hospital cardiopulmonary arrest. J Emerg Trauma Shock [serial online] 2012 [cited 2020 Jul 4];5:338-41. Available from: http://www.onlinejets.org/text.asp?2012/5/4/338/102405



   Introduction Top


Out-of-hospital cardiopulmonary arrest (OHCPA) is a devastating disease process with neurological injury accounting for a disproportionate amount of the morbidity and mortality following the return of spontaneous circulation (ROSC). [1] The neurological injury is caused by a direct ischemic insult and a global cerebral ischemia-reperfusion injury following successful resuscitation from OHCPA. The global cerebral ischemia-reperfusion injury is induced by an inflammatory response, increased intracellular levels of glutamate, an excitatory neurotransmitter released from presynaptic terminals, activation of ion-channel complexes that cause calcium to shift from the extracellular to the intracellular fluid, leading to the accumulation of oxygen free radicals and the activation of degradative enzymes. [1],[2]

The global cerebral ischemia-reperfusion injury also induces the expression of Heme oxygenase 1 (HO-1). [3] The HO-1, a ubiquitous inducible stress-response protein, serves a major metabolic function in heme turnover. HO-1 activity cleaves heme to form biliverdin-IX, endogenous carbon monoxide (CO), and iron, which play a concerted action in cytoprotection against oxidative stress and in the modulation of cell proliferation and differentiation. [4],[5] At low concentrations, exogenous CO can confer cyto and tissue-protective effects similar to those associated with endogenous HO-1 expression, including antioxidative, anti-inflammatory, antiproliferative, and antiapoptotic effects. [6] Experimentally, CO can ameliorate ischemia-reperfusion injury in neurons, the heart, lung, kidney, liver, small intestine and limbs. [6],[7],[8],[9],[10],[11],[12] In addition, blood carboxyhemoglobin is an indicator of the endogenous production of CO by the HO-1 and exogenous inhaled CO. [13] However, no study has investigated the carboxyhemoglobin level associated with cardiopulmonary arrest (CPA). Therefore, this study retrospectively investigated the significance of the level of carboxyhemoglobin following an OHCPA.


   Materials and Methods Top


This study was a retrospective chart analysis and it was approved by the Institutional Review Board in National Defense Medical College Hospital.

This hospital has been able to analyze blood carboxyhemoglobin and methemoglobin levels using a blood gas analyzer (ABL 520 Radiometer R , Copenhagen, Denmark) since 2005 because this machine automatically measured the pH, PO 2 , PCO 2 , HCO3 - , base excess (BE), carboxyhemoglobin, and methemoglobin. This study conducted a medical chart review of patients treated from January 2005 to December 2005. The inclusion criteria included patients who were transported to this department due to OHCPA. The exclusion criteria included patients who did not undergo blood gas analysis on arrival and those that experienced OHCPA due to acute carbon monoxide intoxication by carbon monoxide exposure.

The subjects were divided into two groups based on their final outcome as survival or non-survival. The following variables measured at the time of the patients arrival were analyzed by a review of medical charts in the two groups: sex; age; witness of collapse; bystander cardiopulmonary resuscitation (CPR); electrocardiogram at scene (ventricular fibrillation (Vf) or not); cause of CPA (trauma or non trauma); state on arrival (out of hospital ROSC: OH-ROSC or CPA on arrival CPAOA); total ROSC; pH; PO 2 ; PCO 2 : HCO3 - ; base excess (BE); carboxyhemoglobin and methemoglobin on arrival.

A statistical analysis was performed using Student's unpaired t-test and the chi-squared test. Differences with P values of less than 0.05 were considered to be statistically significant.


   Results Top


There were 183 patients who were transported to this department due to OHCPA in 2005. Among them, 55 patients, who did not undergo blood gas analysis, were excluded. In addition, three patients who experienced cardiac arrest due to acute carbon monoxide intoxication were also excluded. The remaining 125 patients were defined as subjects in this study. All subjects underwent 10 L/minute of oxygen mask in prehospital setting and tracheal intubation after arrival with the same 10 L/minute of oxygen when a blood gas analysis was performed.

The results of the groups defined by survival are shown in [Table 1]. There was no significant difference associated with the sex, age, frequency of witness collapse, bystander cardiopulmonary arrest, electrocardiogram at scene, cause of CPA, value of PCO 2 , HCO3 - , and methemoglobin. The frequency of the OH ROSC and the value of pH, PO 2 , BE, and carboxyhemoglobin in the survival group were greater than those values in the non-survival group. There were no subjects whose carboxyhemoglobin level was 0% on arrival in the survival groups.

The value of carboxyhemoglobin was 54%, 55%, and 69% in the three excluded acute carbon monoxide intoxication cases. Two of those (54 and 69%) could not obtain ROSC and the other did not survive more than 24 hours after obtaining ROSC.
Table 1: Results based on the survival and non-survival

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   Discussion Top


This is the first report that there appeared to be an association between higher carboxyhemoglobin levels and survival in comparison with the non-survival patients. The level of carboxyhemoglobin at the time of arrival in the emergency room might be important prognostic factor for predicting outcome of OHCPA.

CPA induces a direct ischemic insult and ischemia-reperfusion injury occurs throughout the body after patients achieve ROSC. Endogenous or exogenous CO can ameliorate ischemia-reperfusion injury in multiple organs. [6],[7],[8],[9],[10],[11],[12] The level of blood carboxyhemoglobin has been shown to correlate with the endogenous and exogenous CO levels. [13] Carboxyhemoglobin levels as low as 2% to 6% decrease exercise capacity and induces ischemic ST-segment changes and arrhythmia. [14],[15] A previous study also demonstrated that the value of carboxyhemoglobin is associated with increased mortality among critically ill patients, so that failure to up-regulate the response in the proinflammatory stress phase is deleterious. [13] Therefore, the level of carboxyhemoglobin in OHCPA patients on arrival could be a prognostic factor.

The optimal range for carboxyhemoglobin levels is a clinically important problem. A high level of carboxyhemoglobin, such as acute carbon monoxide intoxication, is lethal. Levels as low as 0.6% to 1.8% may be optimal to allow critically ill patients to survive in the intensive care unit. [13] None of the patients with a carboxyhemoglobin level of 0%, survived or regained consciousness in this study, indicating that 0% carboxyhemoglobin was not optimal value for OHCPA patients to obtain full recovery. While an average value of 1.85% carboxyhemoglobin in the survival group may already have deleterious side effects on the coronary and cerebral functions. Never smokers with a carboxyhemoglobin level in the top quartile (above 0.67%) had a significantly higher incidence of cardiac events and deaths, compared to those with carboxyhemoglobin levels in the lowest quartile (below 0.50%). [16] In addition, according to a multivariate analysis, the carboxyhemoglobin concentration was found to be the only independent predictor of carotid intima-media thickness so that chronic CO exposure may increase the risk of atherosclerotic cardiovascular events. [17] On the contrary, after establishing a cerebral ischemic model using mice by transient middle cerebral artery occlusion and exposing them to different concentrations of CO, Zeynalov demonstrated that low CO levels protected the brain from injury following 90-min transient focal ischemia and 48 h of reperfusion. One explanation for the CO protection in an ischemia-reperfusion protocol was that when CO is given at an early time point, it might limit the surge in free-radical formation following reperfusion. [18] Accordingly, chronic exposure of CO may be increase of ischemic event due to atherosclerotic change even in low concentration of CO. However, when this ischemic event occurs, then a low concentration of CO could work as protective against ischemia-reperfusion injury through anti-free-radical, anti-inflammatory, anti-apoptotic, and vasodilatory mechanism. [19],[20]

Regarding some limitations of this study, we did not assess the smoking status of the subjects because that information was not in the medical records. The carboxyhemoglobin level is a biomarker for cigarette use. [21] The half-life of exogenously delivered CO without supplemental oxygen administration is 5-6 hour. [21] Accordingly, both exogenous (CO inhalation by cigarette use) and endogenous (CO production by HO-1) CO affected the level of carboxyhemoglobin in this study. The pH and BE levels as determined by a blood gas analysis might therefore be more informative factors regarding the prognosis because the smoking history was not found to influence the pH and BE levels. [22] Another limitation is due to the fact that this study was retrospective and it only had a small sample size of the survival group. Hence, further prospective large studies are needed to determine whether the carboxyhemoglobin level can be a prognostic tool in the emergency department or not, while also determining the optimal carboxyhemoglobin levels for OHCPA patients.


   Conclusion Top


There appeared to be an association between higher carboxyhemoglobin levels and survival in comparisons with survival and non-survival patients.

 
   References Top

1.Zacharia BE, Hickman ZL, Grobelny BT, DeRosa PA, Ducruet AF, Connolly ES. Complement inhibition as a proposed neuroprotective strategy following cardiac arrest. Mediators Inflamm 2009;2009:124384.   Back to cited text no. 1
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2.Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557-63.  Back to cited text no. 2
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3.Zhang B, Wei X, Cui X, Kobayashi T, Li W. Effects of heme oxygenase 1 on brain edema and neurologic outcome after cardiopulmonary resuscitation in rats. Anesthesiology 2008;109:260-8.  Back to cited text no. 3
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4.Ryter SW, Choi AM. Heme oxygenase-1/carbon monoxide: From metabolism to molecular therapy. Am J Respir Cell Mol Biol 2009;41:251-60.   Back to cited text no. 4
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5.Barbagallo I, Tibullo D, Di Rosa M, Giallongo C, Palumbo GA, Raciti G, et al. A cytoprotective role for the heme oxygenase-1/CO pathway during neural differentiation of human mesenchymal stem cells. J Neurosci Res 2008;86:1927-35.  Back to cited text no. 5
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6.Ryter SW, Kim HP, Nakahira K, Zuckerbraun BS, Morse D, Choi AM. Protective functions of heme oxygenase-1 and carbon monoxide in the respiratory system. Antioxid Redox Signal 2007;9:2157-73.   Back to cited text no. 6
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7.Biermann J, Lagreze WA, Dimitriu C, Giallongo C, Palumbo GA, Raciti G, et al. Preconditioning with inhalative carbon monoxide protects rat retinal ganglion cells from ischemia/reperfusion injury. Invest Ophthalmol Vis Sci 2010;51:3784-91.  Back to cited text no. 7
    
8.Nakao A, Kaczorowski DJ, Wang Y, Cardinal JS, Buchholz BM, Sugimoto R, et al. Amelioration of rat cardiac cold ischemia/reperfusion injury with inhaled hydrogen or carbon monoxide, or both. J Heart Lung Transplant 2010;29:544-53.   Back to cited text no. 8
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9.Yoshida J, Ozaki KS, Nalesnik MA, Ueki S, Castillo-Rama M, Faleo G, et al. Ex vivo application of carbon monoxide in UW solution prevents transplant-induced renal ischemia/reperfusion injury in pigs. Am J Transplant 2010;10:763-72.   Back to cited text no. 9
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11.Katada K, Bihari A, Mizuguchi S, Yoshida N, Yoshikawa T, Fraser DD, et al. Carbon monoxide liberated from CO-releasing molecule (CORM-2) attenuates ischemia/reperfusion (I/R)-induced inflammation in the small intestine. Inflammation 2010;33:92-100.  Back to cited text no. 11
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12.Li J, Zhu ZL, Qi WZ, Shi ZL. Carbon monoxide inhalation protects against limb ischemia/reperfusion injury. Zhongguo Ying Yong Sheng Li Xue Za Zhi 2010;26:33-6.  Back to cited text no. 12
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13.Melley DD, Finney SJ, Elia A, Lagan AL, Quinlan GJ, Evans TW. Arterial carboxyhemoglobin level and outcome in critically ill patients. Crit Care Med 2007;35:1882-7.  Back to cited text no. 13
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14.Allred EN, Bleecker ER, Chaitman BR, Dahms TE, Gottlieb SO, Hackney JD, et al. Short-term effects of carbon monoxide exposure on the exercise performance of subjects with coronary artery disease. N Engl J Med 1989;321:1426-32.  Back to cited text no. 14
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15.Sheps DS, Herbst MC, Hinderliter AL, Adams KF, Ekelund LG, O'Neil JJ, et al. Production of arrhythmias by elevated carboxyhemoglobin in patients with coronary artery disease. Ann Intern Med 1990;113:343-51.  Back to cited text no. 15
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17.Davutoglu V, Zengin S, Sari I, Yildirim C, Al B, Yuce M, Ercan S. Chronic carbon monoxide exposure is associated with the increases in carotid intima-media thickness and C-reactive protein level. Tohoku J Exp Med 2009;219:201-6.  Back to cited text no. 17
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18.Zeynalov E, Doré S. Low doses of carbon monoxide protect against experimental focal brain ischemia. Neurotox Res 2009;15:133-7.   Back to cited text no. 18
    
19.Leffler CW, Parfenova H, Jaggar JH. Carbon monoxide as an endogenous vascular modulator. Am J Physiol Heart Circ Physiol 2011;301:H1-H11.   Back to cited text no. 19
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20.Otterbein LE. The evolution of carbon monoxide into medicine. Respir Care 2009;54:925-32.  Back to cited text no. 20
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21.Scherer G. Carboxyhemoglobin and thiocyanate as biomarkers of exposure to carbon monoxide and hydrogen cyanide in tobacco smoke. Exp Toxicol Pathol 2006;58:101-24.  Back to cited text no. 21
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22.Yanagawa Y, Sakamoto T, Sato H. Relationship between laboratory findings and the outcome of cardiopulmonary arrest. Am J Emerg Med 2009;27:308-12.  Back to cited text no. 22
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Correspondence Address:
Youichi Yanagawa
Department of Traumatology and Critical Care Medicine, National Defense Medical College, 3-2 Namiki Tokorozawa
Japan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0974-2700.102405

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