American Journal of Emergency Medicine 31 (2013) 1290.e3-1290.e5

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Case Report

Clinical experience with landiolol hydrochloride in conservative management of blunt aortic injury

Abstract

Landiolol hydrochloride (LH) has advantages over other ?-blockers because it has a shorter half-life (4 minutes) and its effects are titratable. In the acute-phase management of blunt aortic injuries (BAI), aggressive blood pressure management, reduction of heart rate, and decreased contractility with the administration of ?-blockers are critical to reduce aortic wall tension. Here we report the first case of the use of LH in the conservative management of BAI. A 41-year-old man riding a motorcycle fell off his vehicle after colliding with a car. Computed tomography showed Arterial extravasation, along with pelvic fractures and an intimal tear at the aortic isthmus. After transcatheter arterial embolization was performed to control bleeding from the left superior gluteal artery, the patient was admitted to the intensive care unit. The patient was treated conservatively because the aortic injury was an intimal tear that was associated with major extrathoracic injuries. After LH administration, heart rate was well controlled at less than 80 beats/ min without a significant decrease in blood pressure. No aneurysm or bleeding appeared on the follow-up computed tomography. The patient was discharged on day 81. Our experience suggests that LH is useful for conservative management of BAI.

Although blunt aortic injuries (BAIs) are traditionally treated with emergency (b 24 hours) Surgical repair, delayed repair (open/endovas- cular) is becoming popular [1]. Patients with associated Major injuries

or those with no severe Associated injuries or major comorbidities

can be safely managed with delayed repair after blood pressure and contractility are adequately controlled. Moreover, definitive nonopera- tive management may be chosen in a hemodynamically stable case after medical therapy, particularly in association with major extra- thoracic injuries [1]. Aggressive blood pressure management along with a decrease in heart rate and contractility with ?-blocker therapy is critical for decreasing aortic wall tension and is essential for Nonoperative management or in the lead-up to delayed surgery [4-7]. Landiolol hydrochloride (LH) and esmolol are 2 commercially available short-acting ?₁-selective blockers. Landiolol hydrochloride (ONOACT; Ono Pharmaceutical, Osaka, Japan) is an ultrashort-acting ? blocker with higher ?₁ selectivity (?₁/?₂ = 255) and a shorter elimination half-life (4 minutes in healthy subjects) than any other currently available ?-blocker [8,9]. We thought that LH would be suitable for medical treatment of BAI with major extrathoracic injuries owing to its high ?₁ selectivity and rapid onset/offset of action. We report the first

case of successful conservative management of BAI using LH.

A 41-year-old man riding a motorcycle fell off his vehicle (2 m away) after colliding with a parked car. He was bleeding from the nose and mouth and was brought to our hospital. On initial examination, his vital signs were as follows: body temperature, 36.1?C; blood pressure, 100/

52 mm Hg; heart rate, 108 beats/min; and respiratory rate, 29 breaths/ min. His peripheral Arterial oxygen saturation under oxygen supple- mentation (10 L/min oxygen via a nonrebreathing mask) was 100%.

His mouth was filled with blood. Therefore, tracheal intubation was performed to protect the airway under sedation with fentanyl and midazolam. Whole-body contrast-enhanced computed tomogra- phy (CT) scan (Figs. 1 and 2) showed extravasations from the left superior gluteal artery along with Pelvic fractures, an intimal tear at the aortic isthmus, a basilar Skull fracture, a blow-out fracture of the left eye, a left Femoral neck fracture, and a dislocated left hip.

After transcatheter arterial embolization was performed to control bleeding from the left superior gluteal artery, the patient was admitted to the intensive care unit. The Abbreviated Injury Scale scores were as follows: head/neck, 3; face, 2; thorax, 4; abdomen, 0;

extremities, 3; external, 0; and injury severity score, 34.

The patient was treated conservatively because the aortic injury was an intimal tear with associated major extrathoracic injuries. Blood pressure was maintained at less than 120 mm Hg, and heart rate was well controlled, with a target rate of less than 80 beats/min. We evaluated volume status by collapsibility of the inferior vena cava as detected by echocardiography, urine output, and urine-specific gravity. Fluid loading was performed when hypovolemia was detected. Pain was managed by continuous infusion of fentanyl (1-1.5 ug kg^-1 h^-1). Midazolam (10 mg/h) was used for sedation, and the patient was controlled at the level of -2 to -3 on the Richmond Agitation-sedation score Scale. The patient developed fever up to 38?C on admission day 1 but was kept under observation, and the fever subsided the next day.

Follow-up CT scans on admission days 2 and 5 showed no fresh aortic aneurysm or progressive aortic dissection. open reduction and internal fixation were performed for the left femoral neck fracture on day 8, and the patient was transferred to the general ward on day 13. His subsequent hospital course was stable (Fig. 3). He recovered well after rehabilitation and was discharged on day 81. No apparent aortic aneurysm or progressive aortic dissection was observed during the 3- year outpatient follow-up.

We report a case of BAI that was safely managed medically by pharmacologically controlling blood pressure, heart rate, and contrac- tility with LH. Landiolol hydrochloride is a newly developed, short-acting ?-blocker with high ?₁ selectivity and a short half-life (4 minutes), which has 8-fold higher cardioselectivity than esmolol [10-12]. Moreover, the inhibitory effect of LH on Cardiovascular performance is significantly lower than that of esmolol at equipotent ?-blocking doses [11].

In the acute phase of severe trauma, the heart rate is influenced by several factors such as hypovolemia caused by Massive bleeding, pain, anxiety, fever, and sympathetic activation. Therefore, close monitor- ing of vital signs and volume status, along with echocardiography, is mandatory during ?-blocker administration [13,14].

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B

A

Fig. 1. Chest CT scan on admission. A and B, Arrow shows intimal tear at the aortic isthmus.

A

B

Fig. 2. Computed tomography scan on admission. A, head CT scan shows basilar skull fracture, blow-out fracture of the left eye, and fracture of the nose. B, Arrow shows extravasation from the left superior gluteal artery.

Fentanyl (50 ?g/h)

Fentanyl (75 ?g/h )

Midazolam (10 mg/h)

Landiolol (10 ?g/kg/min)

Landiolol (6 ?g/kg/min)

140 6000

120 5000

100

HR (/min), SBP (mmHg)

80

60

40

20

0

4000

In - out balance (ml/day)

3000

2000

1000

0

-1000

1 2 3 4 5 6 7

Hospital day

In - out balance (ml/day)

HR (/min)

SBP

(mmHg)

Fig. 3. Hospital course. SBP, systolic blood pressure; HR, heart rate.

T. Hifumi et al. / American Journal of Emergency Medicine 31 (2013) 1290.e3-1290.e5 1290.e5

We started LH in intensive care unit on the day of admission. Heart rate was controlled at less than 80 beats/min without a significant decrease in blood pressure, and stable hemodynamics were main- tained with LH administration and fluid management. We initially administered LH at 10 ug kg^-1 min^-1, titrated to 6 ug kg^-1 min^-1 to control heart rate at less than 80 beats/min. A dosage of 10 to 40 ug kg^-1 min^-1 is recommended for managing postoperative supraven- tricular tachycardia [15,16], and a lower dose may be sufficient to manage trauma, with a target heart rate of 80 beats/min. Larger doses of LH would be required if the heart rate needs to be controlled at 60 to 80 beats/min, as advocated by Kepros et al [4].

To minimize aortic wall stress, a target systolic blood pressure less than 120 mm Hg has been advocated by Mattox and Wall [17], whereas 100 to 110 mm Hg was proposed by Hirose et al [6]. Although antihypertensives were not required in our case, nitroprusside and/or a Calcium-channel blocker could have been added for blood pressure control if needed [6]. However, these drugs have much longer elimination half-life than LM and should be used with great caution during the acute phase in patients with trauma.

Complications related to LH use were not observed in our patient; therefore, it seems to be safe. Although the current case involved nonoperative management, LH can be useful in the acute phase of management with delayed repair. Further study is required for detailed evaluation of the clinical benefits of LH in patients with BAI.

Toru Hifumi MD Ichiro Okada MD Nobuaki Kiriu MD Hiroshi Kato MD Junichi Inoue MD Yuichi Koido MD

Department of Critical Care Medicine and Trauma, National Hospital Organization Disaster Medical Center, Tachikawa, Tokyo, Japan

E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2013.03.044

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