Article, Neurology

A new marker identification of high risk stroke patients: Jugular saturation

a b s t r a c t

Objectives: The aim of this prospective study; to investigate in emergency patients with stroke the rela- tionship between jugular saturation and National Institutes of Health Stroke Scale , lesion volume and mortality score.

Materials and methods: In this prospective study, 82 patients who fulfilling the criteria for inclusion in diagnosed with were enrolled in the study. Patients’ demographic data, comorbid conditions and stroke type were recorded. The arterial blood pressure, heart rate, and consciousness were recorded at the emer- gency department. Glasgow coma score and National Health Institutions Stroke Scale (NIHSS) scores were calculated. complete blood count and biochemical values were obtained at the time of admission to the emergency department. Arterial blood gas and jugular venous blood gas were taken and pO2, SpO2 and lactate values were recorded. Patients were grouped according to jugular desaturation (<50%). After imaging, the lesion was located by a specialist radiologist and the lesion volume was calcu- lated. Afterwards, it was followed up by means of the hospital registry system where the patients were followed up (service, intensive care), hospitalization time and whether in-hospital mortality occurred. Results: 82 patients were included in the study. Of the 82 patients, 36 (43.9%) were male and 46 (56.1%) were female. The mean age was 69.8 +- 13.3. Patients were divided into two groups, jugular venous sat- uration <50% and >=50%. 16 patients with J.SpO2 <50% were detected. There was no difference between the two groups in terms of age, sex, Glasgow Coma Scale (GCS), National Health Institutions Stroke Scale (NIHSS) score, laboratory data other than hemoglobin and lesion volume (p > 0,05). In-hospital mor- tality occurred in 9 (13.6%) of patients with J.SpO2 >=% 50; In the group with J.SpO2 < % 50, 6 patients (37.5%) died within the hospital and this difference was statistically significant (p < 0,05).

Conclusion: SjVO2 measurement can be used to identify high-risk stroke patients and to direct critical interventions. However, no correlation was found between this value and lesion volume and NIHSS scale.

(C) 2019

Introduction

Stroke is a clinical picture of vascular origin, developing without any cause and encountered with focal or generalized cerebral dys- function, which may sometimes be temporary or permanent, sometimes with mortality [1]. As a cause of death, it is responsible for 15% of total deaths in Turkey, as well as all over the world [2].

q The authors have no disclosures or conflicts of interest.

* Corresponding author at: Department of Emergency Medicine, University of

Health Sciences, Konya Education and Research Hospital, Konya 42090, Turkey.

E-mail address: [email protected] (M. Guven).

Approximately 85% of stroke cases are ischemia and 15% are hemorrhages [3,4]. Despite all the advances in the medical world, mortality rates in the first 30 days are 8-20% in ischemic stroke and 30-55% in hemorrhagic stroke [5].

Jugular venous oxygen saturation (SjVO2) is an important indi- cator of the balance between global cerebral oxygen delivery and metabolic need [6]. SjVO2 is used to monitor patients who are at risk of developing hypoxia or cerebral ischemia, as well as to adjust the ventilation applied to decrease intracranial pressure, to deter- mine the increase of Intracranial hypertension, to diagnose arteri- ovenous fistula and to show the progression to brain death [7,8]. Studies on SjVO2 have generally been concentrated on patients

https://doi.org/10.1016/j.ajem.2019.03.040 0735-6757/(C) 2019

with severe Cerebral injury due to trauma. We planned to investi- gate the relationship between jugular saturation and GCS, NIHSS score, lesion volume and mortality in patients admitted to the emergency department with stroke diagnosis.

or sections obtained throughout the structure was multiplied by the distance between the sections, i.e. the cross-sectional thick- ness. This process was expressed by the following formula:

V : t * (a1 + a2 + +an)

Materials and methods

In the formula, (a1 + a2 +

+ an) expresses the cross-sectional

The study was planned in the Emergency Department of Konya Education and Research Hospital in Health Sciences University. This emergency service is a tertiary emergency department serving 360,000 patients annually. Patients admitted to the Emergency Medicine Clinic between November 2016 and June 2017 and diag- nosed with Ischemic or hemorrhagic stroke were included in the study. Ethics committee permission was obtained from the local ethics committee.

Patient selection

The study was planned to include non-pregnant patients over 18 years of age and with stroke. Patients under the age of 18, those radiological evaluation“>pregnant, those with low O2 saturation, those who could not lie on their back, those with bleeding diathesis and non-consenting patients were planned to be excluded. Patients eligible for throm- bolytic therapy were excluded from the study. Samples were taken from the patients included in the study from the jugular vein by ultrasonography to analyze the venous blood gas.

Outcome measures

The patients’ demographic data, comorbid conditions and stroke types were recorded. Arterial blood pressure was taken at the time of admission to the emergency department. Glasgow Coma score and National Health Institutions Stroke Scale (NIHSS) scores were calculated. Full blood and biochemical values were obtained at admission to the emergency department. Arterial

surface areas as cm2, and (t) shows the cross-sectional thickness of successive sections in n number as cm.

2.4. Statistical analysis

Statistical analysis was performed on the SPSS for windows 15.0 software. The conformity of the variables to normal distribution was examined by visual (histogram and probability graphs) and analytical (Kolmogorov-Smirnov/Shapiro-Wilk tests) methods. Descriptive analyzes were expressed as mean +- SD for normally distributed variables, median and interquartile range (IQR) for non-normally distributed variables. Categorical data were com- pared with chi-squared or Fisher exact test.

The relationship between the jugular saturation obtained and lesion location, insular cortex and thalamus involvement, right or left lobe involvement, anterior or posterior circulation obstruction and lesion volume were investigated. Patients were divided into two groups according to the Jugular saturation value as below 50% and above 50%. In the comparisons between these two groups, Mann-Whitney U was used for normal data, and chi-squared or Fisher exact test was used for the categorical data. The relationship between jugular saturation and GCS, NIHSS and lesion volume was evaluated by spearman’s correlation test. p-Values below 0.05 were evaluated as statistically significant results.

Table 1

Demographic characteristics of patients.

blood gas and jugular venous blood gas values were obtained and

pO2, SpO2, pH and lactate values were recorded. If SjVO2 was below 50%, jugular desaturation was accepted; patients were grouped according to Jugular desaturation.

After imaging, the lesion location was determined by a special- ist radiologist and the lesion volume was calculated. Insular lobe involvement, thalamus involvement, tentorial or supratentorial localization and anterior or posterior circulation involvement were determined.

Afterwards, it was followed up by means of the hospital registry system where the patients were followed up (service, intensive care), hospitalization time and whether in-hospital mortality occurred.

Radiological evaluation

CT images were taken with 64-detector multi-slice Philips Bril- liance V2.6.1 (2007) and 16-detector Toshiba Activion V3.00 (2010) devices. In both CT devices, standard CT scan parameters were used in 1 mm slice thickness, 1.25 pitch, 120 kV and automatic mAs protocol.

Diffusion MRI examinations were performed with a 1.5-tesla MRI device (MAGNETOM Avanto, Siemens, Erlangen, Germany). diffusion-weighted imaging and ADC mapping (TR: 4000, TE: 102, Slice Range: 5 mm, Matrix: 256 x 256 pixel, FOV: 250 mm) were obtained.

In our study, the Cavalieri principle, the basis of many of the volume calculation methods frequently used in stereology, was used to calculate the volume of the lesion according to CT images. In order to obtain a neutral volume calculation by the Cavalieri method, the sum of the cross-sectional surface areas of the slices

Age, years, mean +- SD 69,8 +- 13,3

Sex, n (%)

Male 36 (43,9)

Female 46 (56,1)

GCS, median (IQR) 15 (2)

NIHSS, median (IQR) 3 (5)

Stroke type, n (%)

Infarct 73 (89)

Hemorrhage 9 (11)

CAD, n (%) 14 (17,1)

DM, n (%) 23 (28)

Hypertension, n (%) 51 (62,2)

CRF, n (%) 3 (3,7)

Lesion location, n (%)

Right hemisphere 42 (51,2)

Left hemisphere 26 (31,7)

Bilateral 14 (17,1)

Insular cortex involvement, n (%) 22 (26,8)

Thalamus involvement, n (%) 30 (36,6)

Tentorial location, n (%) 14 (17,1)

Anterior circulation n (%) 59 (72)

Glucose, mg/dL, median (IQR) 131 (68)

Urea, mg/dL, median (IQR) 39 (21)

Creatinine, mg/dL, median (IQR) 0,9 (0,3)

White blood cell, 103/mm3, mean +- SD 9,2 +- 2,8

Hemoglobin, g/dL, median (IQR) 13,7 (3)

Arterial SpO2, median (IQR) 95 (3)

arterial lactate, mmol/L, median (IQR) 1,1 (0,8)

JSpO2, median (IQR) 65,5 (24)

Jugular lactate, mmol/L, median (IQR) 1,6 (0,9)

In-hospital mortality 15 (%18,3)

1 month mortality 10 (%12,2)

JSpO2: jugular saturation, GCS: Glasgow Coma Score, IQR: interquartile range, NIHSS: National Health Institutions Stroke Scale, CAD: coronary artery disease, DM: diabetes mellitus, CRF: chronic renal failure, JSpO2: jugular saturation.

Results

A total of 82 patients were included in the study. Of the 82 patients, 36 (43.9%) were male and 46 (56.1%) were female. The mean age was 69.8 +- 13.3 years. Demographic data of the patients are shown in Table 1.

The NIHSS score was median (IQR) 3 [5], the GCS score was median (IQR) 15 [2]. Of the cases included in the study, 73 (89%) were infarct and 9 (11%) were hemorrhage. The lesion was located on the right side in 42 (51.2%) of these cases, on the left side in 26 (31.7%) and on both sides in 14 (17.1%). Insular cortex involvement was detected in 22 cases (26.8%). In 30 cases (36.6%), thalamus involvement was detected. 14 cases (17.1%) were detected in the tentorial region and 68 cases (83.9%) in the supratentorial region. 59 cases (72%) were caused by anterior circulation and 23 (28%) by posterior circulation. 15 cases (18.3%) died in the hospital, while 10 cases (12.2%) died in one month.

The arterial saturation of the patients was median (IQR) 95% [3] and the jugular saturation was median (IQR) 65.5% [24] mm Hg. Jugular desaturation was detected in 16 (19.5%) of the patients.

There was no significant difference in SjVO2 when insular cor- tex involvement was compared in terms of tentorial or supratento- rial location and anterior or posterior irrigation area (p > 0.05). SjVO2 was found to be 68.8 +- 15.7 in the lesions containing thala- mus and 61.7 +- 16.5 in the lesions without thalamus (p = 0.057). No correlation was found in SjVO2 between NIHSS, GCS and lesion volume (p > 0.05).

The patients were divided into two groups as jugular venous saturation <50% and >=50%. 16 cases were detected with J.SpO2

<50%. J.SpO2 <50% of the group were all ischemic stroke. No differ- ence was found between these two groups in terms of age, gender, blood pressure, GCS, NIHSS score, arterial saturation, laboratory data other than hemoglobin and lesion volume (p > 0.05). The com- parison of the two groups is shown in Table 2.

Table 2

Comparison of 2 groups according to jugular desaturation.

While in-hospital mortality occurred in 9 (13.6%) of the patients with J.SpO2 >= 50%, it occurred in 6 (37.5%) of the patients with J.SpO2 < 50%, and this difference was found to be statistically significant (p < 0.05).

Discussion

This is a prospective study investigating the prognostic value of jugular desaturation in patients with stroke. According to the results of this study, jugular desaturation is associated with mor- tality in stroke cases.

Stroke is the second cause of death constituting 15% of total deaths in Turkey as well as all around the world [2]. Mortality rates in the first 30 days are 8-20% in ischemic stroke and 30-55% in hemorrhagic stroke. Approximately 50% of deaths occur in the first 2 days and 6% before reaching the hospital [5].

Physiologically, brain perfusion is determined by the consump- tion demand corresponding to the adequate supply of nutrients and oxygen. Jugular venous oxygen saturation is an important indi- cator of the balance between global cerebral oxygen delivery and metabolic need [6]. Jugular venous oxygen saturation is a monitor- ing method used in patients with risk of hypoxia and cerebral ischemia and reflects the use of cerebral oxygen [9,10]. The mea- surement is done with a catheter placed in the jugular bulbus. SjVO2 is used to monitor patients who are at risk of developing hypoxia or cerebral ischemia, as well as to adjust the ventilation applied to decrease intracranial pressure, to determine the increase of intracranial hypertension, to diagnose arteriovenous fistula and to show the progression to brain death [7,8]. Therapeutic hyper- ventilation has been reported to be beneficial in patients with intracranial hypertension. However, hypoperfusion may develop due to hypocarbia after this maneuver. SjVO2 monitoring has been reported to be an important method of follow-up in order to avoid this situation [11].

Studies conducted in the literature are continuous jugular venous saturation follow-up studies with the help of a catheter in intensive care conditions [12,13]. Our study was obtained by evaluating the blood sample taken from the jugular vein in the

J.SpO2 < %50

(n = 16)

J.SpO2 >= % 50 p (n = 66)

emergency department at admission.

De Deyne et al. reported that persistent brain damage may

Age, years, median (IQR) 74 (22) 70 (15) 0,712

Sex, male, n (%) 8 (22.2) 28 (77.8) 0,58

GCS, median (IQR) 12 (6) 15 (2) 0,85

NIHSS, median (IQR) CAD, n (%)

DM, n (%)

4,5 (10)

3 (3,7)

5 (6,1)

3 (4)

11 (13,4)

18 (22)

0,143

0,54

0,48

ments in the outcome [12]. In another article, it was emphasized that attentive follow-up and Timely intervention in patients with

HT, n (%)

7 (8,5)

44 (53,7)

0,09

acute brain injury can help prevent secondary brain injury on a

CRF, n (%)

2 (2,4)

1 (1,2)

0,09

large scale [14].

occur if desaturation cannot be defined and appropriately man- aged. There is evidence indicating that intervention in desaturation status with early SjVO2 monitoring is associated with improve-

Studies on jugular desaturation in the literature are studies on severe head trauma. We have not yet found any study on ischemic

Arterial saturation, median (IQR)

93 (4)

95 (2)

0,09

SBP, mm Hg, median (IQR)

135 (28)

145 (40)

0,38

DBP, mm Hg, median (IQR)

70 (20)

80 (20)

0,43

Glucose, mg/dL, median (IQR)

124 (88)

131 (67)

0,734

or hemorrhagic stroke. In a study conducted by Fandino J. et al., 50

Urea, mg/dL, median (IQR)

39,5 (30)

39 (21)

0,958

trauma patients were examined and SjVO2 monitoring was shown

Creatinine, mg/dL, median (IQR)

1 (0,6)

0,9 (0,3)

0,395

to be a method that can be used to detect neurological damage

J.SpO2: jugular saturation, IQR: interquartile range, GCS: Glasgow Coma Score, NIHSS: National Health Institutions Stroke Scale, CAD: coronary artery disease, DM: diabetes mellitus, HT: hypertension, CRF: chronic renal failure, SBP: systolic blood pressure, DBP: diastolic blood pressure, MCA: Middle cerebral artery. Bold values statistically significance at p < 0.05.

WBC, 103/mm3, median (IQR)

8,7 (5,9)

9 (2,3)

0,578

Hemoglobin, g/dL, median (IQR)

12 (2)

14 (2,3)

0,006

Lesion volume, cm3, median (IQR)

2,9 (27,1)

4,3 (18,2)

0,884

Insular cortex involvement, n (%)

5 (6,1)

17 (20,7)

0,75

Thalamus involvement, n (%)

3 (3,7)

27 (32,9)

0,14

MCA irrigation area, n (%)

3 (3,7)

7 (8,5)

0,4

Tentorial location, n (%)

10 (12,2)

49 (59,8)

0,35

Admission to ICU, n (%)

8 (9,8)

48 (58,5)

0,08

In-hospital mortality, n (%)

6 (37,5)

9 (13,6)

0,027

1 month mortality, n (%)

5 (31,3)

5 (7,6)

0,009

[15]. In a study by Gopinath et al., patients with excessive desatu- ration episodes and patients without desaturation episodes were compared and patients with excessive desaturation episodes were found to have worse neurological damage [6].

Buunk et al. measured SjVO2 after cardiac arrest in 30 comatose patients and found a significant relationship between mortality and SjVO2 values [16]. In the studies conducted by Croughwell et al. on 255 patients, it was reported that the consciousness states of the patients after resuscitation were related to desaturation [17,18].

In the study conducted by Garlick et al., desaturation episodes were more frequent and longer in the Neurological sequelae secondary to head trauma [19]. In another study, desaturation

episodes were shown to be common in patients with severe head trauma and it was emphasized that follow-up and good manage- ment of these episodes would decrease the mortality rate [20]. In a study conducted by Cruz et al. on 28 patients with acute brain injury, patients with SjVO2 monitoring were followed up, a signif- icant relationship was found between mortality and poor neuro- logical outcome in patients with and without desaturation, and a significant increase was reported in survival rates after appropriate intervention in patients with desaturation [13].

In our study, in-hospital mortality was recorded and two groups were formed as SjVO2 < 50 and SjVO2 >= 50. Desaturation was found in 19.5% of the patients included in our study and mortality occurred in 37.5% of these patients. Mortality occurred only in 13.6% of patients without desaturation. A statistically significant difference was found between these two groups. Jugular saturation measurement can be used to identify high-risk stroke as well as head trauma. There was also a significant difference between these two groups in terms of hemoglobin values. In the study by Shein- berg et al., it was reported that if SjVO2 was low, hemoglobin should be increased above 9 mg/dL [20]. Therefore, the prognosis of the patients can be improved with the interventions to be per- formed in patients with low jugular saturation and can be used to guide the treatment.

SjVO2 measurement was expressed in previous studies that reflect the balance between cerebral oxygen delivery and cerebral oxygen consumption [21]. This definition naturally raises the rela- tionship between Sjvo2 and Cerebral autoregulation. Cerebral autoregulation is a physiological event in which various mecha- nisms are introduced in order to achieve a constant cerebral blood flow by changing the mean blood pressure. This prevents neuronal damage. One of the situations in which autoregulation mecha- nisms are inadequate is called spreading depolarization [22].SD can cause by stroke, subarachnoid hemorrhage head trauma and migraine and it is a state of continuous neuronal depolarization [23]. As a result of the increase of neurotransmitters such as gluta- mate and acetylcholine, the intracellular and extracellular ion bal- ance changes and a negative potential dominates for an average of 1 min [24]. An increase in the consumption of oxygen and glucose occurs. This is the 1st phase of SD. Vasoconstriction and hypoper- fusion prevail. Hyperemia occurs in cerebral tissue with the intro- duction of many vasodilators in Phase 2. However, increased cerebral blood flow cannot meet the metabolic needs and oxygen demand, and tissue hypoxia develops. The last phase is an oligemic period which takes approximately 1 h. Vascular reactivity decreased. And ultimately cerebral ischemia occurs. The occur- rence of SD in penumbra was associated with increased infarct area [22,24].

Robertson and colleagues examined 177 patients with severe

head trauma. Jugular desaturation episodes were observed in 7 of 22 patients who were monitored by microdialysis. They found that the concentration of glutamate increased from 11.5 +- 8.5 to 55 +- 10.4 mol/L [21]. Both SD and jugular desaturation use same pathophysiological pathways which are associated with increased glutamate levels. This can be thought as the hypothesis of different reflections of the same pathophysiological ways. We believe that studies evaluating SD and jugular saturation may shed light on this issue. Thus, new monitoring methods and new treatment modali- ties may be developed to maintain cerebral resuscitation. For example, hypoxia can cause the onset of SD, and also SD can cause hypoxia [24]. Previous oxygen therapy has been shown to not affect outcome in stroke [25,26]. However, the effectiveness of oxygen therapy in patients with low jugular saturation may be evaluated by new randomized controlled trials. It may also con- tribute to the formation of different research areas for the develop- ment and monitoring of new drugs effective at the receptor level.

In the analysis of these two groups, 8 (9.8%) of the patients with J.SpO2 < 50% were hospitalized and the other 8 (9.8%) were admit- ted to the intensive care unit. While 48 (58.4%) of the patients with J.SpO2 >= 50% were hospitalized, 18 (22%) were admitted to the intensive care unit (p = 0.08). Although the p value did not reach the significance level, further and more comprehensive studies can investigate the predictivity of SjVO2 in the intensive care triage.

Conclusion

SjVO2 measurement can be used to identify high-risk stroke patients and to guide critical interventions. However, no correla- tion was found between this value and lesion volume and NIHSS scale. The relationship between SjVO2 and cerebral autoregulation is among the issues to be investigated.

Limitations

Our study is the first study on a group of patients with CVA. However, it also had some limitations. The first one was the small number of cases. Therefore, factors affecting mortality could not be investigated by advanced statistical methods. Because of the majority of patients with low median NIHSS scores, they may have masked the association of patients with severe NIHSS scores and lesion volume with jugular saturation. The second limitation was that only mortality was obtained as the endpoint of our study, and the neurological sequelae of the patients at discharge could not be evaluated. Our third limitation was that we could not per- form continuous saturation monitoring, so the presence and dura- tion of desaturation episodes and their effects on the results are not known. In addition, findings such as perfusion findings and penumbra size were not comparable with jugular desaturation. The possible association of jugular desaturation and poorly per- fused areas will allow new studies for thrombolytic therapy as well as cerebral resuscitation interventions.

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