a b s t r a c t

Aim: We assessed out-of-hospital cardiac arrest patients’ cerebral oxygenation during cardiopulmonary resuscitation (CPR) using near infrared spectrophotometry (NIRS). We evaluated the relation between a rise in patients’ cerebral saturation values between the start and end of CPR and return of spontaneous circulation. Materials and methods: Twenty-three patients with unwitnessed out-of-hospital cardiac arrest and brought to our emergency department by emergency ambulance were evaluated. cerebral saturations from time of start of CPR were measured using NIRS. CPR was performed for a maximum of 30 min. The relation between cerebral saturations in patients with or without return of spontaneous circulation was then evaluated.

Results: Twenty-three patients, 12 (52.2%) female and 11 (47.8%) male, with a mean age of 64.09 +- 13.66 were included. A correlation was determined between a rise in cerebral saturation measured throughout CPR and the return of spontaneous circulation (P b .001).

Conclusion: Patients whose cerebral saturation values measured with NIRS rise during CPR have a higher post- resuscitation survival rate. Monitoring of patients during CPR with this Non-invasive technique may be a good method for predicting return of spontaneous circulation.

Introduction

Despite the development of successful Resuscitation techniques, the survival rate among out-of-hospital cardiac arrest patients is still low [1]. Successful resuscitation means not only achieving spontane- ous circulation, but also the oxygenation of vital organs. The most cerebral oximetry)”>important cause of death in arrest patients is central nervous system injury [2]. The use of cerebral oximetry to assess brain oxygenation has risen in recent years. Near infrared spectrophotometry (NIRS) is particularly used to evaluate cerebral oxygenation in cardiovascular surgery [3]. NIRS measures total oxygen saturation in a specific volume of tissue by approximately evaluating the hemoglobin oxygen saturation fraction inside the terminal vascular network of the brain tissue bed. Low measurements or initial measurements decreasing indicate ischemia or hypoxia in the brain tissue [4].

This technology can be used to assess cerebral oxygenation during CPR and in follow-up. Constant monitoring of cerebral perfusion with this technique can elicit important therapeutic information. Pro- longed hypoxia in brain tissue increases mortality in arrest patients.

* Corresponding author. Recep Tayyip Erdogan University Faculty of Medicine, Department of Emergency Medicine, 53020 Rize/Turkey. Tel.: +90 464 217 0366; fax:

+90 464 217 0367.

E-mail address: [email protected] (K. Asim).

We think that low cerebral oxygenation measured using NIRS may indicate that patients have a low level of return of spontaneous circulation. It also suggests greater brain damage. The purpose of this study was to determine whether or not spontaneous circulation had returned by evaluating the cerebral saturation of patients with out-of- hospital cardiac arrest.

NIRS (cerebral oximetry)

Cerebral oximetry is a neurological monitoring technique devel- oped for adult and pediatric surgery in the 1970s. The technology is still used today in areas such as non-cardiac surgery cardiology, resuscitation, and trauma [5]. The INVOS-5100c COx device utilizes NIRS technology to measure mixed venous-arterial (70/30) oxygen saturation in the frontal lobes of the cerebral cortex. This primarily venous oxygen saturation level is a function of local tissue oxygen consumption and therefore oxygen delivery, making the measure- ment a reliable reflection of perfusion. Each probe consists of an adhesive strip housing a single near-infrared light transmitter and 2 sensors, allowing penetration of the skin, skull, and cortical brain tissue. Using two sensors, light is scattered by the tissues in two parabolic curves measuring hemoglobin saturation of the blood from the skin and skull in one sensor, and from the skin, skull, and frontal cortex tissue in the other. Frontal cortex hemoglobin saturation is

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K. Asim et al. / American Journal of Emergency Medicine 32 (2014) 14-17 15

calculated by subtraction of the two signals. Limits of detection for the device include a hemoglobin-oxygen saturation of b 15% or N 95% and a cortical tissue depth of N 2 cm [6].

Cerebral saturation (SCO2) values in normal healthy individuals range between 55 and 75. When SCO2 values rise more than 25% above basal values during monitoring with NIRS in cardiovascular surgery, cerebral ischemia is suspected and appropriate measures are taken [7].

Materials and methods

Study design and setting

This study was performed at the Recep Tayyip Erdogan University Medical Faculty Emergency Medicine Department, Turkey, between January and June, 2013. The local ethical committee approved the study protocol before commencement. Written consent forms were received from the relatives of all the patients included. Our hospital emergency department (ED) admits approximately 120,000 patients annually. Approximately 100 to 150 of these patients brought to the ED with cardiac arrest arrive by ambulance. Since the urban settlement area is small (~ 250 km²), all cardiac arrests cases reach our ED quickly and in a short time (~ 10 minutes), with the provision of basic life support-advance life support as required in compliance with the European Resuscitation Council guidelines 2010.

Participants

Thirty patients with a mean age of 64.09 +- 13.66 (mean+-SD) years (21-82 years) brought in by the emergency ambulance service after unwitnessed out-of-hospital arrest were included. Seven patients were subsequently excluded due to diagnosis of cerebrovascular event at post-traumatic autopsy. The emergency medical service team included a doctor and a paramedic. They provided CPR to the patients in accordance with European Resuscitation Council Guidelines 2010 on site and during transport as required prior to admission to the ED. No mechanical compression device was employed. Only patients without pulse, despite having received CPR prior to admission to hospital ED, were included in this study. Admitted patients lacking spontaneous circulation continued to receive CPR by the emergency staff. The duration of the cardiac arrest before resuscitation was not determined. Monitoring with cerebral oximetry was provided as soon as the CPR team started resuscitation. CPR in line with the advanced cardiac life support American Heart Association 2010 guideline was administered to all patients. Duration of CPR was determined as a maximum 30 minutes. Cerebral saturations were monitored until patients were declared dead or until spontaneous circulation returned.

Cerebral oximetry measurements

Advanced life support was provided for each patient with arrest. Circulation was absent from all the patients brought in. Patients were met by a 6-member resuscitation team in the ED. The team consisted of 2 doctors, 2 nurses, and 2 paramedics. One of the nurse task was to monitor and record cerebral saturation. Recording was performed with an INVOS 5100C cerebral/somatic oximeter (Covidien). The oximeter probes were attached appropriately above the muscles in the frontal region. Recording took place throughout resuscitation. NIRS was not applied before admission because of possible discon- nection after unsuccessful CPR interventions.

Statistical analysis

Descriptive statistics are presented as frequency, percentage, mean, standard deviation and median, minimum and maximum values. Fisher exact test or the Pearson ?² test were used in the analysis of relations between categorical variables. The Mann-

Table 1

Patient characteristics and demographic data

Characteristics Number (%)

Age (mean +- SD) 64.09 +- 13.66

Male 11/23 (47.8)

Initial rhythm VF 11/23(47.8)

Initial rhythm asystolic 9/23 (39,1)

Initial rhythm PEA 3/23 (13)

Full recovery 7/23 (30.4)

Whitney U test was used in the analysis of differences between the 2 groups’ measurement values. Receiver operating characteristic (ROC) analysis was performed in the calculation of sensitivity, specificity and Area under curve values of specific variables in differentiating surviving or non-surviving patients. Odds ratios with a 95% confi- dence interval were set in comparing risk of death of groups determined on the basis of determined cut-off points. P b .05 were regarded as significant. Analyses were performed using SPSS 18.00 (SPSS, Chicago, IL).

Results

Twenty-three out-of-hospital cardiac arrest patients with a mean age of 64.09 +- 13.66 (mean +- SD) were included in the study. Twelve patients (52.2%) were female and 11 (47.8%) male. CPR in line with American Heart Association resuscitation rules was administered to all patients. Spontaneous circulation was established in 7 (30.4%) patients, but not in the other 16 (69.6%). Pulseless electrical activity (n = 3, 13%), ventricular fibrillation (n = 11, 47.8%), and

asystolic rhythms (n = 9, 39.1%) were determined when the patients were brought to our ED (Table 1).

Together with restoration or otherwise of spontaneous circulation, mean SCO2 and the levels of increase in these values were compared during CPR. Patients’ cerebral oxygenations were measured from the right and left frontal regions. The median of the highest SCO2 values of the patients in whom spontaneous circulation was established was

68.86 (min: 43 max: 93), while the median of the lowest SCO2 values was 18 (range, 15-47). Median of the rise in SCO2 values in the right frontal region in restoration of spontaneous circulation with CPR was 52 (range, 17-77), and the median left frontal region value was 50 (range, 11-74). Median of the highest SCO2 values in the right frontal region in patients in whom circulation could not be established was

24.5 (range, 15-49), and that of the lowest values was 15 (range, 14- 31). Mean increase in SCO2 values after CPR was halted and death declared was 5 (range, 0-18) in the right frontal region and 3 (range, 0-20) in the left. The highest SCO2 values and the increase in SCO2 values in the right and left frontal lobes were significantly higher in the patients in whom spontaneous circulation was restored compared to the others (P b .001). No statistically significant difference was determined between the lowest right and left lobe SCO2 values (P N

.05) (Table 2). Spontaneous circulation was established in patients with a rise in SCO2 values, but not in patients with no rise.

Table 2

NIRS data and levels of increase measured during CPR

Variable	Survival	Survival	P
	NO (% min-max)	YES (% min-max)
Highest right SCO2 (%)	24.5 (15-49)	68.86 (43-93)	b.001
Highest left SCO2 (%)	22.5 (14-53)	68 (53-92)	b.001
Lowest right SCO2 (%)	15 (14-31)	18 (15-47)	b.356
Lowest left SCO2 (%)	17 (13-33)	18 (17-52)	b.268
Level of right frontal SCO2 increase (%)	5 (0-18)	52 (17-52)	b.001
Level of left frontal SCO2 increase (%)	3 (0-20)	50 (11-74)	b.001

16 K. Asim et al. / American Journal of Emergency Medicine 32 (2014) 14-17

Table 3

Analysis of patients’ glucose and blood gas value by return of otherwise of spontaneous circulation

Discussion

Those patients in our study with out-of-hospital cardiac arrest

Variable General Survival No

Survival Yes

P with a rise in SCO2 during CPR had a higher survival rate than those with no rise. Survival could not be achieved in patients with low

Glucose 198 (75-658) 171 (75-467) 302 (156-658) .038*

Blood has Ph 7.01 (6.83-7.33) 7.01 (6.85-7.33) 7.04 (6.83-7.27) .763

PCO2 56.0 (26-76) 55.5 (26-76) 56.0 (27-72) .841

PO2 69.0 (40-135) 64.5 (40-110) 97.0 (58-135) .038*

There was a statistically significant difference in blood glucose levels between patients whose spontaneous circulation was restored and the others. Median blood glucose level in patients with Restored spontaneous circulation was 302 (156-658) g/dL and

171 (75-467) g/dL in patients in whom spontaneous circulation was not restored (P = .038). Patients’ arterial blood basses were measured at the start of CPR. There was no correlation between blood pHs and survival (P N .05). There was no statistically significant difference between surviving and non-surviving patients in terms of PaCO₂ measurements (P N .05). However, a correlation was determined between PaO₂ measurements and survival (P =

.038). Patients with restored spontaneous circulation had higher PaO₂ values than those without (Table 3).

ROC analysis was performed in differentiating surviving and non- surviving patients on the basis of the variables set out in Table 4. At the analyses, a cut-off value of 16% was determined for rises in SCO2 levels in the right frontal region and 20% in the left frontal region. Patients with a rise in SCO2 of <=16% in the right frontal region had a 4.504-fold greater risk of not surviving compared to patients with more than 16%. Patients with a rise of <=20% in the left frontal region had a 9-fold greater risk of non-survival than patients with more than 20%. The probability of the SCO2 value in the right frontal lobe of the 16 non-surviving patients exhibiting a rise of 16% and less than 16% is 87.5% (sensitivity), while the level for the 20% cut-off point in the level frontal lobe is 100%. The risk of non-survival of patients with a glucose value of <=198 is 13 times greater that that of the patients with a value N 198, while the risk of non-survival of patients with a PO₂ value <=66 is 10 times greater than that of patients with a value greater than 66. Sensitivity for the cut-off point determined for glucose on the basis of these values is 68.8%, specificity 85.7%, and for PO₂ sensitivity is 62.5% and specificity 85.7%. Since AUC values that express success in predicting survival on the basis of cut-off points determined for amounts of increase in patients’ right and left frontal lobe SCO2 were greater than 80%, these markers are suitable for predicting survival.

cerebral saturation values and exhibiting no increase. This is the first study to evaluate the relationship between return or otherwise of spontaneous circulation and changes in cerebral saturations in patients with pre-hospital cardiac arrest. Various studies in the literature support our ideas. In a case series involving 5 patients, Frish et al used NIRS to measure tissue saturations in patients with pre- hospital cardiac arrest and suggested that patients with low values had a higher possibility of re-arrest. They compared tissue saturation with end-tidal carbon dioxide levels and reported that NIRS measurements predicted arrest in an earlier period. In contrast to our study, in which cerebral saturation was determined, they measured tissue saturation with NIRS [8]. Tissue saturation and cerebral saturation are measured on the same principles. We think that the fact that cerebral saturation was measured in our study represents an advantage over Frish et el.’s study. In an experimental study, Reynolds et al reported that End-tidal carbon dioxide values did not decrease immediately in pigs with induced ventricular fibrillation, but that tissue saturation fell by 28% in 1 min. They suggested that NIRS monitoring is a reliable technique in patients with pre-hospital cardiac arrest. They thus suggested that NIRS could be used in predicting re-arrest. Even experienced resuscitators are known to lose time looking at pulse rates in arrest patients. That study therefore emphasized that they could establish that patients were in re-arrest easily with NIRS monitoring than looking at pulse rates [9]. In our study, cerebral saturations measured using NIRS rising by more than 16% in the right frontal lobe and by more than 20% in the left frontal lobe in patients brought in with cardiac arrest was determined as a predictor or return of spontaneous circulation. A fall in tissue saturation in arrest patients reported in Reynolds et al.’s study and a rise in cerebral saturations in patients with restored spontaneous circulation are findings parallel to our own. One advantage of our study is that it involved humans.

NIRS is used to monitor trends in changes in cerebral perfusion in

other Disease states. There are several studies in both the surgical and intensive care literature showing that SCO2 has good prognostic abilities [10,11]. These studies assessed cerebral blood flow using NIRS and brain magnetic resonance imaging and reported that NIRS was as good an imaging technique as magnetic resonance imaging. We think that every minute that the brain is deprived of oxygen is important in patients with out-of-hospital cardiac arrest, and that NIRS is a good

Table 4

ROC analysis data

Parameter	Cut off	Alive	Ex	Odds Ratio 95% CI	AUC	Performance
Level of increase, right	N 16	7	2	4.504	0.938	Sens: 87.5%
Level of increase, left	<=16 N 20	0 5	14 0	(1.326-15.385) 9	P = .001 0.857	Spec: 100% PPV: 100% NPV: 77.8% Sens: 100%
Glucose	<=20 N 198	2 6	16 5	(2.437-33.244) 13	P = .008 0.772	Spec: 85.7% PPV: 88.9% NPV: 100% Sens: 68.8%
PO2	<= 198 N 66	1 6	11 6	(1.239-140.679) 10	P = .042 0.741	Spec: 85.7% PPV: 91.7% NPV: 54.5% Sens: 62.5 %
	<= 66	1	10	(0.957-140.490)	P = .071	Spec: 85.7 % PPV: 90.9% NPV: 50%

Sens, sensitivity; Spec, specificity; PPV, positive predictive value; NPV, negative predictive value.

K. Asim et al. / American Journal of Emergency Medicine 32 (2014) 14-17 17

method of determining how much the brain is affected and of predicting survival.

Nardi et al.’s study showed that Tissue oxygenation measured with NIRS in patients with sepsis hospitalized in the intensive care unit being low or tending to fall was associated with a decrease in hospital discharge rates and an increase in Death rates [12]. In addition, low tissue oxygen saturation has been reported as a marker of increased mortality according to sepsis guidelines [13]. Spontaneous circulation could not be achieved in patients with an increase below cut-off values in our study. Multi-center studies with larger patient numbers will provide useful information in predicting survival in patients administered CPR. Parameters such as the patient being young and having a shockable rhythm are used in predicting survival [14]. In our view, NIRS data are also a valuable means of predicting survival.

Post-arrest cell death usually takes place in 4 to 8 minutes. Even if spontaneous circulation is restored in these patients, it may not be possible to restore cerebral circulation. Several studies have reported that the use of hypothermia and neuroprotective agents is appropriate in order to reduce neurological injury to a minimum [15-18]. Another limitation of our study is that neuroprotective agents and hypother- mia were not used.

Conclusions

The best way of increasing discharge from hospital after arrest is still providing basic life support and advanced cardiac life support in the best manner. In conclusion, monitoring patients with this non- invasive technique may be a good method of predicting return of spontaneous circulation.

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