Pre-hospital portable monitoring of cerebral regional oxygen saturation (rSO2) in seven patients with out-of-hospital cardiac arrest

In recent years, measurement of cerebral regional oxygen saturation (rSO2) has attracted attention during resuscitation. However, serial changes of cerebral rSO2 in pre-hospital settings are unclear. The objective of this study was to clarify serial changes in cerebral rSO2 of patients with out-of-hospital cardiac arrest (OHCA) in the pre-hospital setting. We recently developed a portable rSO2 monitor that is small (170 × 100 × 50 mm in size and 600 g in weight) enough to carry in pre-hospital settings. The sensor is attached to the patient’s forehead by the ELT (Emergency Life-saving Technician), and it monitors rSO2 continuously. From June 2013 through August 2014, serial changes in cerebral rSO2 in seven patients were evaluated. According to the results of the serial changes in rSO2, four patterns of rSO2 change were found, as follows. Type 1: High rSO2 (around about 60 %) type (n = 1). Initial electrocardiogram was ventricular fibrillation and ROSC (return of spontaneous circulation) could be diagnosed in pre-hospital setting. Her outcome at discharge was Good Recovery (GR). Type 2: Low rSO2 (around about 45–50 %) type (n = 3). They did not get ROSC even once. Type 3: Gradually decreasing rSO2 type (n = 2): ROSC could be diagnosed in hospital, but not in pre-hospital setting. Their outcomes at discharge were not GR. Type 4: other type (n = 1). In this patient with ROSC when ELT started cerebral rSO2 measurement, cerebral rSO2 was 67.3 % at measurement start, it dropped gradually to 54.5 %, and then rose to 74.3 %. The cerebral oxygenation was impaired due to possible cardiac arrest again, and after that, ROSC led to the recovery of cerebral blood flow. We could measure serial changes in cerebral rSO2 in seven patients with OHCA in the pre-hospital setting. Our data suggest that pre-hospital monitoring of cerebral rSO2 might lead to a new resuscitation strategy.


Background
In recent years, measurement of cerebral regional oxygen saturation (rSO 2 ) by near-infrared spectroscopy (NIRS) has attracted attention in many fields [1][2][3][4]. We thought that it might be useful for the development of a new resuscitation strategy. Some research groups have reported that cerebral rSO 2 on hospital arrival can predict neurological outcome in patients with out-of-hospital cardiac arrest (OHCA) [5,6], but we thought this might not be correct because the values of rSO 2 always change depending on the patient's situation at the time cerebral rSO 2 is measured [7]. Some research groups have reported that serial changes of cerebral rSO 2 in hospital cardiac arrest patients may reflect high-quality cardiopulmonary resuscitation (CPR) [8,9]. We hypothesised that rather than measuring one rSO 2 value at one time point, measurement of serial changes in the values of rSO 2 would be important. To prove this hypothesis, pre-hospital measurement of rSO 2 in patients was needed. We recently developed a portable rSO 2 monitor that is small enough to carry in pre-hospital settings. In this study, we tried to detect the serial changes of rSO 2 measured by the Emergency Life-saving Technician (ELT) in earlier phase after out-of-hospital cardiac arrest. The objective of this study was to clarify serial changes in cerebral rSO 2 of patients with out-of-hospital cardiac arrest in the pre-hospital setting.

Study design and data collection
The subjects were all cardiopulmonary arrest (CPA) patients who were transferred to the National Hospital Organization Osaka National Hospital (Osaka, Japan) by ELTs based at Chuo Fire Station. The ELTs performed CPR according to recommendations of the Japan Resuscitation Council Guidelines 2010, which are based on the guidelines of the American Heart Association and the International Liaison Committee on Resuscitation [10]. The rSO 2 sensor is attached to the patient's forehead by the ELT (Fig. 1a). Medical staff did not change patient treatment according to rSO 2 data.
The pre-hospital portable monitoring of cerebral rSO 2 in CPA patients with OHCA was approved by the Ethics Committee of Osaka University Graduate School of Medicine (No. 12446), and the institutional review board waived the need for informed consent because the subjects were all in CPA.

Portable NIRS rSO 2 monitoring system
We developed a portable rSO 2 monitor (HAND ai TOS ® ; TOSTEC CO., Tokyo, Japan) (Fig. 1b). The HAND ai TOS was not approved by Medicines and Healthcare Products Regulatory Agency (MHRA) and Food and Drug Administration (FDA). The HAND ai TOS system measures oxygen saturation based on the Beer-Lambert law by using three different wavelengths of near-infrared LED light, which have specific absorbance to oxyhaemoglobin and deoxyhaemoglobin. The lights pass through the skin to a depth of approximately 3 cm, and the reflected lights are sensed by a photodiode. The reflected lights represent the haemoglobin information mainly in the cerebral cortex. The system can measure rSO 2 data every second without the necessity of arterial pulsation, so it is possible to carry out continuous monitoring in CPA patients. Two rSO 2 values, left side and right side, are acquired continuously, and then the average of the two values is calculated. The normal range of cerebral rSO 2 was previously determined from 15 healthy adult volunteers to be 71.2 ± 3.9 % (on room air) (n = 15, 10 men and 5 women, 43.2 ± 8.9 years) [7].

Statistical analysis
All data are represented as mean ± standard deviation (SD). All statistical analyses were performed with JMP Pro 10 for Windows (SAS Institute Inc., Cary, NC, USA).

Fig. 1
Photograph showing rSO 2 measurement in a mock patient by ELTs and the portable near-infrared spectroscopy unit (portable rSO 2 monitor). a The detector consists of two sensors that monitor the bilateral frontal lobes. The ELT can carry the portable rSO 2 monitor (HAND ai TOS ® ; TOSTEC CO., Tokyo, Japan) and perform cardiopulmonary resuscitation without difficulty in the pre-hospital setting. b The portable rSO 2 monitor is 170 × 100 × 50 mm in size and 600 g in weight. It can be carried easily by hanging it around the neck, and it can be used even in severe pre-hospital environments such as heavy rain and strong sunlight. rSO 2 regional saturation of oxygen; ELT emergency life-saving technician

Patient characteristics
From June 2013 through August 2014, serial changes in cerebral rSO 2 in seven patients were evaluated. Characteristics, outcome, and rSO 2 data of the OHCA patients are shown in Table 1. According to the results of the serial changes in rSO 2 , four patterns of rSO 2 change were found, as follows. Type 2 (low rSO 2 type [n = 3]) is shown in Fig. 2b (Table 1; patient #6). Her initial ECG was asystole. The rSO 2 values remained at around 50 %. Her GOS outcome at discharge was death. A similar rSO 2 pattern was observed in patients #5 and #7 (Table 1; Additional file 1: Figure S1B, C), whose ECGs also showed asystole. The mean value of cerebral rSO 2 at the start of measurement was 49.3 ± 3.8 %. None of these patients attained ROSC even once.  Figure S1A). ROSC was diagnosed inhospital in patient #2 but not in the pre-hospital setting. The GOS outcome of patient #2 was also death.  Fig. 2d. In this patient with ROSC when the ELTs started cerebral rSO 2 measurement, cerebral rSO 2 at measurement start was 67.3 % (almost normal range), it dropped gradually to 54.5 %, and it then rose to 74.3 %. Her cerebral oxygenation was impaired due to possible return of cardiac arrest, and after that, ROSC led to the recovery of cerebral blood flow. Her GOS outcome at discharge was vegetative state.

Discussion
In this report, we showed the pre-hospital serial changes of cerebral rSO 2 in patients with OHCA. The values of cerebral rSO 2 in the patients with OHCA dramatically changed in the very early phase after cardiac arrest.
Our data showed several advantages of the pre-hospital measurement of cerebral rSO 2 . First, we might be able to predict the neurological outcome of patients with VF. The initial ECGs of patients #1 and #2 both showed VF, but the initial rSO 2 value of patient #1 was higher than that of patient #2 (Table 1; Fig. 2a, c). In terms of neurological outcome, patient #1 experienced good recovery, whereas that of patient #2 was death (Table 1). Our report suggested that a patient who maintained a high cerebral rSO 2 value might have a good neurological prognosis, and the type of serial change in the pre-hospital cerebral rSO 2 data might lead to the prediction of neurological outcome in patients with VF.
Second, the pre-hospital cerebral rSO 2 data might allow the estimation of the time after cardiac arrest in unwitnessed cases. Presence of a witness is one of the factors of good neurological prognosis [11,12], but if witness information is absent, we might treat CPA patients as those for whom considerable time had passed after CPA. We could detect gradually decreasing cerebral rSO 2 in two patients (Fig. 2c). We thought that the gradually decreasing rSO 2 type probably indicated that little time had passed since CPA. To better understand the relation between time and cerebral rSO 2 , it will be necessary to accumulate data from more witnessed CPA patients. Third, a portable rSO 2 monitoring system would be very useful, similar to ECG monitoring, for ELTs in the pre-hospital setting. As shown in Fig. 2d, dynamic changes of cerebral rSO 2 can be revealed. When the value of cerebral rSO 2 decreased in Fig. 2d, the ECG showed QRS waves. We determined that pulseless electrical activity could be diagnosed at that time. The ELTs cannot always check the patient's pulse in the pre-hospital setting, especially when they are transporting the patient on stairs or into the ambulance, because they must transfer the patient to hospital quickly. By using our portable rSO 2 monitor, ELTs can always check cerebral blood flow without actually having to check the pulse.
Finally, the presence of a continuous low rSO 2 type might predict poor neurological outcome and high mortality.
Our report has some limitations. First, rSO 2 monitoring was not performed in a blind fashion. Therefore, rSO 2

Fig. 2
Serial changes in cerebral rSO 2 (representative cases). a Type 1: High rSO 2 type (around 60 %). One patient (51-year-old woman; patient #1) showed this type. Her initial electrocardiogram was ventricular fibrillation, and ROSC was diagnosed in the pre-hospital setting. Her outcome at discharge was good recovery. b Type 2: Low rSO 2 type (around 45-50 %). Three patients (52.7 ± 30.2 years, 1 man and 2 women) showed this type. This graph shows the serial changes in cerebral rSO 2 of patient #6. A similar pattern was observed in patients #5 and #7. None attained ROSC even once. c Type 3: gradually decreasing rSO 2 type. Two patients (69.5 ± 6.4 years, 2 men) showed this type. Serial changes in cerebral rSO 2 from patient #4 are shown. The rSO 2 value gradually decreased. ROSC was diagnosed in-hospital 35 min after the start of measurement. His outcome was death. A similar pattern was also observed in patient #2. Both patients attained ROSC, which was diagnosed in hospital but not in the pre-hospital setting. Their outcomes at discharge were death. d Type 4: other type. One patient (86-year-old woman; patient #3) showed this type. In this patient with ROSC, when the ELT started cerebral rSO 2 measurement, the cerebral rSO 2 was 67.3 %. It dropped gradually to 54.5 % and then rose to 74.3 %. Cerebral oxygenation was impaired due to possible return of cardiac arrest, but after that, ROSC led to the recovery of cerebral blood flow. The shaded area represents the normal cerebral rSO 2 range measured from healthy adults. rSO 2 regional saturation of oxygen, ROSC return of spontaneous circulation, ELT emergency life-saving technician value may influence CPR procedures. Second, the validation of HAND ai TOS about low rSO 2 value (<60 %) had been demonstrated in vitro but not in vivo. Third, sample size is small. To generalize this results, we need further study in a larger population.

Conclusion
We could measure serial changes in cerebral rSO 2 in seven patients with OHCA in the pre-hospital setting. Further evaluation of the validity of pre-hospital monitoring of cerebral rSO 2 may lead to a new resuscitation strategy in the pre-hospital setting.