Ischemic stroke is a non-communicable disease characterized by a sudden neurological deficit due to thrombotic or embolic event that disrupts blood flow in the brain. Disruption of blood flow due to the thrombotic is generally caused by a blood clot obstructed on blood vessels. This condition is usually related to atherosclerosis, artery dissection, etc. Furthermore, disruption of blood flow due to embolic occurs as a result of breaks of a blood clot that enters the bloodstream [1,2]. The American Stroke Association stated that 87% of cases were caused by ischemic stroke [2]. World Stroke Organization also reported over 12.2 million cases of a new onset of stroke in people aged >15 years old each year [3]. The largest proportion (62%) of the population who experience a stroke are people aged 50–69 years old [3]. The total number of ischemic stroke cases is 7.6 million each year, with 58% of cases occurring in people under the age of 70 years old [3]. According to the Riset Kesehatan Dasar (Riskesdas) 2018, it was stated that the prevalence of stroke in people aged >15 years old in Indonesia reached 713,783 people, 55.3% of whom are people who live in urban areas. Meanwhile, the proportion of people aged >75 years old has the highest stroke incidence rate with a percentage of 50.2% [4].

Centers for Disease Control and Prevention also stated that after age >55 years old, the chance of experiencing stroke will double every ten years [5]. One of the clinical conditions that is at risk of increasing the incidence of stroke in the elderly is hypertension. Hypertension usually has a strong relation with structural and mechanical changes in the walls of blood vessels. Structural and mechanical changes in blood vessels due to the aging process, especially arterial blood vessels, cause a decreased elasticity of blood vessels. This condition can increase systolic and diastolic blood pressure. Because of this mechanism, the elasticity of blood vessels is used as a predictor of cardiovascular disease and stroke [6,7].

Traveling by air transportation, such as airplanes and helicopters, also can increase the risk of stroke [8-10]. Mendes et al. [11] (2023) reported a 60-year-old man who experienced recurrent stroke when traveling by commercial flight. It was known after that the passenger didn’t have a fit-to-fly certificate due to a new onset of transient ischemic attack (TIA), seven hours before the flight. A new onset of TIA attack showed a worsening of neurological deficit. This condition led to an emergency landing at the nearest airport. The recurrence of stroke in this case can be caused by various factors related to environmental changes during in-flight. Additionally, in this case, the passengers also broke the recommendation from the International Air Transport Association (IATA). Based on IATA, TIA patients should only fly within two days after the onset of TIA, with an assessment from a doctor [12]. IATA also recommended that someone who has experienced a stroke is deemed fit to fly, and should be accompanied by a nurse if there is an improvement in symptoms within 5–14 days after the stroke diagnosis is established. Accompaniment by a nurse may not be necessary if the recovery process doesn’t result in complications. It is emphasized that stroke patients flying within two weeks after a stroke attack must use oxygen supplementary during the trip [12]. The risk of recurrence of stroke within 30 days after the first ischemic stroke attack is 3% to 10% [13].

One of the physiological changes during flight related to the risk of ischemic stroke is hypobaric hypoxia [13-15]. The occurrence of hypoxia hypobaric due to changes in high altitude can lead to a reduction in oxygen-rich blood flow to the brain which causes damage up to permanent cell death in the brain.

In addition to hypobaric hypoxia, changes in high altitude also induce changes in G-force [13,16]. G-force is the gravitational force for every acceleration or deceleration that induces an adaption to the changes of this G-force. Normally, G-force on the earth’s surface is 1 G. Three types of G-force to describe the direction and pressure of acceleration are Gz, Gx, and Gy. Gz is a G-force axis that moves vertically upwards (+Gz) from feet to head and vertically downwards (–Gz) from head to feet. Gx consisted of two types, +Gx and –Gx. +Gx is a G-force axis that moves forward (transversal and supine), and –Gx moves backward (transversal and prone). Gy also consisted of two types, +Gy move to the right and –Gy move to the left [13,16,17].

When the commercial aircraft is ready to take off, it will pitch upwards or nose-up at an angle of 50 degrees from the ground surface and experience Gz ranging from 1.5 G to 1.8 G. The G-force that occurs during take-off is +Gx. After reaching a certain altitude, the commercial aircraft will fly horizontally with a small angle and experience a Gz on 0 G. Meanwhile, during the landing process, commercial aircraft will pitch downward with an angle of 50 degrees and experience Gz ranging from 1.5–1.8 G. G-force that occurs during landing is –Gx [18,19].

The changes of G-force during the take-off and landing process, especially –Gz, will reduce the blow flow following the gravitational force resulting in the accumulation of blood in the legs. This condition can pose a risk of clot formation that may detach and enter the bloodstream. The entry of clot formation to the bloodstream can result in impairment of blood flow. If the clot manages to block the blood flow in the brain, it can lead to ischemic stroke [15].

Based on this description, it is controversial whether a person with a history of ischemic stroke who has been declared fit to fly still has a risk of recurrent stroke during in-flight or not. The purpose of this study is to determine the possibility of clinical condition deterioration and/or a new onset of recurrent stroke in commercial flight passengers with history of ischemic stroke related to hypoxia hypobaric during in-flight or post-flight.

1. Clinical Scenario

A 63-year-old man traveling by air transportation accompanied by his family using a commercial flight (travel time 4 hours 20 minutes) complained of severe headaches (visual analogue scale [VAS] 7/10) and suddenly awoke from sleep accompanied by worsening weakness in the left side of the limbs approximately 20 minutes before the plane landed at the local airport.

Vital signs indicated BP 140/70 mmHg and 160/90 mmHg (measured twice), HR of 80 beats per minute, RR of 22 breaths per minute, and Oxygen Saturation of 96% with room air. Upon landing, the headache scale decreased (VAS 5/10) but weakness of the left side of the limbs persisted. The patient was promptly taken to the local hospital’s emergency room, where he was diagnosed with a recurrent stroke, considering his history of ischemic stroke with blockage in the right cerebral blood vessels. Previous treatment had been received at the hospital, and initial physical and neurological examination revealed weakness in the left limb with a motor strength of 5-4//5-4. After a 7-day treatment period, the patient was discharged as symptoms had improved and he was prescribed Aspilet 1^×80 mg, Bisoprolol 1^×10 mg, and Ranitidine 2^×150 mg.

Ten days later the patient consulted with a specialist in aviation medicine to obtain a letter of fitness to fly. Referring to IATA recommendations, doctors allow patients to fly on commercial aircraft accompanied by family.

2. Clinical question

Does the condition of commercial flight passengers with history of ischemic stroke related to hypoxia hypobaric due to high altitude will be worsening during in-flight or post-flight? (Table 1)

3. Methods

1) Search strategy and selection

We searched PubMed, EMBASE, Cochrane, and Ingenta Connect library databases to identify all published studies about the effect of hypobaric hypoxia on commercial flights on clinical conditions in passengers with history of ischemic stroke. The inclusion criteria for our study were passengers aged more than 40 years old. Any studies related to the military aircraft were excluded (Fig. 1).

2) Critical appraisal

We use the Oxford Centre of Evidence-Based Medicine Level of Evidence to appraise the relevance and validity of our selected papers [20]. All of the selected papers will be ranked by their level of evidence (Table 2).

4. Results

Based on the search process from four databases, we procured 73 articles that matched the selected keywords. However, after further review based on the inclusion and exclusion criteria, we only selected three articles potentially matched with the assigned Population/Patients, Intervention, Comparison, Outcome (Table 3-5).

We conducted a critical review of the three articles, all of which were identified as prognostic with cohort study design. The literature search revealed two prospective cohort studies and one retrospective cohort study.

The first article is a study written by Imam et al. [8] a retrospective study conducted in Qatar in 2022. This study was conducted by collecting medical record data of stroke patients referred from the airport to Tertiary Stroke Care Center. The subjects of this study were stroke patients referred to the Tertiary Stroke Care Center, and they were commercial flight passengers, and compared to the non-flight passenger group. The data of the patient group were collected from the database from 1 January 2014 until 1 March 2020, meanwhile, the non-flight group data were collected on 1 January 2018 until 1 March 2020. This study aimed to see the proportion of stroke cases related to flight, the related risk factors, the mean of the flight duration, and the outcome. The study concluded that 43 stroke patients were commercial flight passengers, with a mean age of 59.5 years old and 69.8% were men. The mean of the flight duration in the patient group was 6.6 hours. The types of stroke that occurred were ischemic stroke (69.8%), hemorrhagic stroke (20.9%), and TIA (7%). 34.9% of cases were happened during 1 to 3 hour onset. Also, 54.8% of the cases had good outcomes.

The second study was written by Reynold et al. [10] in 2014. It is a retrospective cohort study with 77 patients diagnosed with TIA or ischemic stroke with carotid artery lesions. This study aims to have a better understanding of the incidence rate of stroke or any symptoms related to stroke in flight or during the 24 hours after flight. The result of this study was there were no incidences of stroke nor the appearance of stroke-related symptoms in-flight and during 24 hours after flight. The mean of the flight durations was 107.1 minutes. Based on the flight duration and the type of the airplane, the authors estimated the cabin pressure changed around 12 psi during the flight, and the estimated alveolar PO2 change was 107 to 76 mmHg.

The third article is a study written by Álvarez-Velasco et al. [9], a retrospective cohort study held in Spain. This study was held for around 76 months, from January 2008 to April 2014. The subjects of this study were patients with ischemic stroke or TIA referred to tertiary hospital. The patients were recruited in January 2008. The outcome of this study were stroke risk factors, history of other diseases, flight duration, onset, and National Institutes of Health Stroke Scale score of the patients. This study aimed to see the prevalence of reported stroke cases related to flight and focused on “economy class stroke” symptoms. The result of the study was that 32 passengers had ischemic stroke and 12 had TIA episodes, 60% of the cases happened during long haul flights (>4 hours), 70% of the cases happened during the flight and most of the cases had a good prognosis.

Based on the three articles we reviewed above, the results were quite varied, however, the outcomes are good for passenger with a history of ischemic stroke, especially for the second study, which have a study population with resembling similarity compared to our scenario. In this study, the authors did not find any ischemic stroke signs and symptoms during flight and 24 hours post-flight. All of the studies above are cohort studies, unfortunately, these studies did not fulfill the importance aspects of the tool we used. However, these studies are the highest reference source we could acquire to answer our clínical question. Even though these studies could not fulfill the importance aspect, the characteristics of the patients in these studies are quite similar to our clinical scenario.

Based on the three articles we reviewed above, we concluded that a new onset of ischemic stroke and clinical deterioration on commercial flight passengers with ischemic stroke history have a good outcome. It means that they didn’t have any clinical condition deterioraation and/or a new onset of ischemic stroke while in-flight or post-flight. These articles have good validity, but there were some limitations of the studies. Thus, further research needs to be done to ensure the clarity of the result.

None.

Conceptualization: ADR, MDS, RH. Writing the original draft: ADR, MDS, RH. Critical revision of article: FA. Final approval of the article: FA. Overall responsibility: ADR, MDS, RH, FA.