Hemostasis is critical for adequate anatomical visualization during endoscopic endonasal skull base surgery. Reduction of intraoperative bleeding should be considered during the treatment planning and continued throughout the perioperative period. Preoperative preparations include the optimization of comorbidities and cessation of drugs that may inhibit coagulation. Intraoperative considerations comprise anesthetic and surgical aspects. Controlled hypotension is the main anesthetic technique to reduce bleeding; however, there is controversy regarding its effectiveness; what the appropriate mean arterial pressure is and how to maintain it. In extradural cases, we advocate a mean arterial pressure of 65–70 mm Hg to reduce bleeding while preventing ischemic complications. For dealing intradural lesion, controlled hypotension should be cautious. We do not advocate a marked blood pressure reduction, as this often affects the perfusion of neural structures. Further reduction could lead to stroke or loss of cranial nerve function. From the surgical perspective, there are novel technologies and techniques that reduce bleeding, thus, improving the visualization of the surgical field.
Endoscopic surgery is a minimally invasive technique that has found a niche in all surgical fields. Endoscopic endonasal surgery ranges from basic and relatively straightforward procedures (e.g., endoscopic septoplasty, endoscopic turbinoplasty, and functional endoscopic sinus surgery) to advanced surgery (e.g., endoscopic orbital and/or optic nerve decompression, endoscopic dacryocystorhinostomy, and endoscopic endonasal skull base approaches). Its advantages are obviating external scars, reducing damage to normal tissue and bone, and shortening recovery time and length of hospital stay. However, intraoperative bleeding presents a larger obstacle to endoscopic visualization. Blood obscures the anatomy of the surgical field and dirties the endoscope lens causing greater difficulty with visualization. This situation increases the risk of complications, including brain injury, orbital or optic nerve injury, and catastrophic bleeding from major vessels (e.g., internal carotid artery).
We advocate careful consideration of all factors regarding the control of bleeding throughout the entire perioperative period. Preoperative preparations include the optimization of co-morbidities and cessation of drugs that may increase the tendency for bleeding. Intraoperative considerations comprise anesthetic and surgical aspects. Some anesthetic aspects are controversial including the use of controlled hypotension and whether inhalation-based or intravenous-based technique is most effective in reducing intraoperative bleeding. Additionally, novel surgical technologies, materials, and techniques help to improve the quality of surgical visualization. This paper aims to review controversies and current concepts regarding how to minimize intraoperative bleeding in endoscopic endonasal skull base surgery. We classify endoscopic endonasal skull base surgery into extradural and intradural surgery. The principles of extradural surgery are similar to those of the endoscopic sinus surgery.
Coagulation comprises three major components: vascular compartment, platelets, and coagulation factors [
Various causes of bleeding tendency.
Components | Causes |
---|---|
Vascular | Inherited Disorder |
(i) Hereditary hemorrhagic telangiectasia | |
(ii) Ehlers-Danlos syndrome | |
Autoimmune disorder | |
Allergic purpura | |
Reduce the integrity of the blood vessel wall | |
(i) Advanced age | |
(ii) Prolonged steroid use | |
(iii) Vitamin C deficiency | |
| |
Platelets | Chronic diseases |
(i) Kidney failure | |
(ii) Liver disease: hepatitis, cirrhosis, and liver failure | |
(iii) Splenic sequestration | |
(iv) Hematologic malignancy: leukemia, lymphoma, and multiple myeloma | |
(v) Bone marrow diseases | |
(vi) Human immunodeficiency virus/acquired immunodeficiency syndrome | |
(vii) Rare autosomal recessive disorders (Glanzmann’s thrombasthenia and Bernard-Soulier syndrome) | |
Autoimmune diseases | |
(i) Idiopathic thrombocytopenic purpura | |
(ii) Systemic lupus erythematosus | |
Medications | |
(i) Antiplatelet: aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) | |
(ii) Antibiotic including penicillin, quinine, and sulfa | |
Dietary supplements | |
Vitamin E, fish oil, | |
| |
Coagulation factors | Inherited disorder |
(i) von Willebrand’s disease | |
(ii) Hemophilia | |
(iii) Other inherited clotting factor deficiencies (factors II, V, VII, X, and XII) | |
Medications | |
(i) Warfarin (coumadin), heparin | |
(ii) Chemotherapies | |
(iii) Vitamin K deficiency | |
Other disorders | |
(i) Autoimmune disorders | |
(ii) Disseminated intravascular coagulation (also results in thrombocytopenia) | |
(iii) Liver disease |
Anamnesis should include symptoms specific to bleeding, such as a history of unexplained bleeding associated with surgical procedures, trauma, or menses, unexplained bruises or hematomas family history suggesting bleeding tendency and use of prescribed and over-the-counter medications and supplements. However, patients may be asymptomatic; therefore, physical examination should investigate the presence of petechiae, ecchymotic lesions, telangiectasias, hepato-splenomegaly, and hemarthrosis of the joints. Furthermore, preoperative laboratory evaluations, including platelet count, prothrombin time, and activated prothrombrin time, are helpful to confirm a suspected diagnosis and for the preoperative planning. However, systematic screening is inefficient and should be confined to patients at high risk [
Identification and preoperative management of patients who are receiving anticoagulants and/or antiplatelet medication cannot be emphasized. Current recommendations include holding both aspirin and clopidogrel for 7–10 days prior to surgery to allow new platelets to replace those that are dysfunctional [
Vascular tumors present a surgical challenge. Preoperative embolization of vascular tumors reduces bleeding, and the need for transfusion, as well as improves the visualization of intraoperative surgical field [
Inflammatory mediators produce diffuse vasodilatation, transudation, and edema in the sinonasal mucosa. Thus, preoperative administration of steroids is beneficial due to their anti-inflammatory and antiedematous effects. These advantages include having a wider nasal corridor, thus, improving visibility of the surgical field. A recent study demonstrated that corticosteroids significantly improved the hemostasis within the operative field (
Controlled hypotension technique includes various modalities associated with different potency and adverse effects. Its safety is dependent on a thorough knowledge about the mechanism of action for each modality, adequate monitoring of the patient, and choosing the appropriate modality with consideration to history of drug allergies and co-morbidities.
Positioning is important for the safety of the patient and to facilitate the surgeon’s ergonomic approach. Reverse Trendelenburg or anti-Trendelenburg position is a common surgical position in which the head is up and feet are down. Head elevation reduces mean arterial pressure in the elevated part by about 2 mm Hg for each 2.5 cm above the cardiac level [
The laryngeal mask airway (LMA) is a supraglottic device that is associated with less respiratory and cardiovascular reflex responses due to reduced stimulation of the larynx as compared to endotracheal intubation. Moreover, LMA facilitates controlled hypotension. One study suggested that LMA is more effective than endotracheal intubation in regard to rapid onset to achieve a target systolic arterial blood pressure (
Ventilation with normocapnia or mild hypocapnia has been advocated to minimize bleeding and optimize the surgical field during endoscopic endonasal skull base surgery. However, a recent study demonstrated no significant difference in the surgical conditions or blood loss among hypocapnia (end tidal carbon dioxide (ETCO2)
Furthermore, mode of ventilation is important to control hypotension. Traditional intermittent positive pressure ventilation (IPPV) has a troublesome hemodynamic effect due to high intrathoracic pressures and reduced venous return to the heart [
Propofol has a depressant effect on the central nervous system via direct activation of the gamma-aminobutyric acid (GABA [A]) receptors, inhibition of the n-methyl d-aspartate (NMDA) receptor, and modulation of the calcium influx through slow calcium ion channels. Propofol has rapid onset of action and recovery time with a dose-related effect. However, dose-dependent hypotension is its most common complication, especially high-dose infusions that are associated with propofol infusion syndrome. This condition is a potentially fatal complication with severe metabolic acidosis and circulatory collapse [
Traditional opioids have been used as analgesic drugs and they bring some hypotensive effect. However, this effect is difficult to use for controlled hypotension due to their long half-life. Remifentanil is a new potent ultrashort-acting
In general anesthesia, opioids are often used as an adjunct of intravenous-based technique (opioids combined with antihypertensive drugs or propofol) or inhalation-based technique (opioids combined with an inhalation agent). There is controversy regarding whether intravenous- or inhalation-based technique is more efficient for controlled hypotension (Table
Comparison of clinical trials study between inhalation-and intravenous-based techniques in controlled hypotension during endoscopic endonasal surgery.
Author (year) | Technique | Mean arterial pressure | Heart rate (beat/min) | Intraoperative bleeding | Surgical field score | Complication | Comment | |
---|---|---|---|---|---|---|---|---|
Ankichetty et al. [ |
Inhalation based: | Iso/Fen | Mean time to achieve target MAP: |
No significant difference | No significant difference |
No significant difference |
No intra- and postoperative complications | No significant difference in sedation score, pain, nausea, vomiting, and hospital stay |
Intravenous based: | Pro/Fen | Mean time to achieve target MAP: |
||||||
| ||||||||
Yoo et al. [ |
Inhalation based: | Sevo/Rem |
Initial: |
|
N/A | 2.21 (1–3) | N/A |
No significant differences of MAP ( |
Des/Rem |
Initial: |
|
N/A | 2.07 (1–3) | N/A | |||
Intravenous based: | Pro/Rem | Initial: |
|
N/A | 2.06 (1–3) | N/A | ||
| ||||||||
Ragab and Hassanin [ |
Inhalation based: | Induction: Pro/Fen |
Mean time to achieve target MAP: |
Decreased by |
Mean |
VAS |
No serious adverse effects in both groups |
(i) Significant difference in time to achieve target MAP and decreased HR ( |
Intravenous based: | Induction: Pro |
Mean time to achieve target MAP: |
Decreased by |
Mean |
VAS |
|||
| ||||||||
Ahn et al. [ |
Inhalation based: | Sevo/Rem | N/A | N/A | 135 mL/h (in patient with high LM score) | Numeric rating scales: |
N/A |
Significant better visualization in the high LM score patients in the intravenous based-group (blood loss |
Intravenous based: | Pro/Rem | N/A | N/A | 19 mL/h |
Numeric rating scales: |
N/A | ||
| ||||||||
Beule et al. [ |
Inhalation based: | Sevo/Fen |
|
|
Mean |
VAS 4.6 |
More impairment of platelet function in intravenous-based group ( |
No significant difference in all parameters ( |
Intravenous based: | Pro/Fen |
|
|
Mean |
VAS 4.9 | |||
| ||||||||
Wormald et al. [ |
|
|
|
|
|
|
|
No significant differences in HR ( |
Intravenous based: |
Pro/Rem |
|
|
N/A |
|
N/A | ||
| ||||||||
Sivaci et al. [ |
Inhalation based: | Induction: Pro |
Initial: |
|
Mean |
N/A | N/A |
(i) Significant lower blood loss in intravenous-based group ( |
Intravenous based: | Induction: Pro |
Initial: |
|
Mean |
N/A | N/A | ||
| ||||||||
Eberhart et al. [ |
Inhalation based: | Iso/Alf | 67 (63–72) mmHg | 72 (66–83) | Estimated blood loss |
VAS 4.9 |
N/A | Significant decreased HR and better visualization in the intravenous based group |
Intravenous based: | Pro/Rem | 65 (61–69) mmHg | 55 (51–64) | Estimated blood loss |
VAS 2.8 |
N/A |
Values are presented as mean ± SD or mean/medians (range); Iso: isoflurane; Sevo: sevoflurane; Des: desflurane; Pro: propofol; Fen: fentanyl; Rem: remifentanil; Esm: esmolol; Alf: alfentanil; VAS: visual analogue score; MAP: mean arterial pressure; HR: heart rate; LM: Lund-Mackay score; N/A: not available;
Review of controlled hypotension series in endoscopic endonasal surgery.
Author (Year) | Target mean arterial pressure | Grading quality of surgical field | Blood loss | Comment | |
---|---|---|---|---|---|
Boezaart et al. [ |
>65 mmHg |
In SNP group* |
In Esm group* |
N/A | The optimum surgical conditions were provided with minimum Esm-induced hypotension (MAP > 65 mmHg); conversely, SNP induced hypotension (MAP 50–54 mmHg) |
| |||||
Jacobi et al. [ |
Moderate controlled hypotension with SNP (65–75 mmHg) |
|
|
(i) Total blood loss and grading quality of surgical field did not show significant difference between the groups | |
Normotensive situation |
|
|
|||
| |||||
Mengistu et al. [ |
Controlled hypotension group 50–55 mmHg | N/A | In Esm group |
Blood loss shows significant difference between the controlled hypotension group and controlled group | |
Controlled group 70–80 mmHg | N/A |
|
SNP: sodium nitropusside; Esm: esmolol; MAP: mean arterial pressure.
Our recommendation allows to maintain MAP at 65–70 mm Hg, to avoid organ hypoperfusion [
There are many methods to deal with intraoperative bleeding during endoscopic endonasal skull base surgery. Their choice often depends on whether the bleeding is from venous or arterial origin, the size of the vessel, and its location [
Controlled bleeding techniques in endoscopic endonasal surgery.
Situation | Source | Technique |
---|---|---|
Artery | ||
Low-flow bleeding |
Small perforating vessels |
Bipolar electrocautery |
Hemostatic biomaterial agents | ||
High-flow bleeding | Medium to large artery | Bipolar electrocautery |
Clips | ||
Angiography embolization | ||
| ||
Venous | ||
Low-flow bleeding | Bleeding from mucosa, bone | Warm saline irrigation |
Focal bleeding from venous sinus | Hemostatic biomaterial agents | |
High-flow bleeding | Venous sinus bleeding | Hemostatic biomaterial agents |
The aim of topical vasoconstrictors is to decongest the nasal cavity, thus widening the nasal corridor and minimizing bleeding. Commonly used topical vasoconstrictors include cocaine, epinephrine, phenylephrine, and oxymetazoline. All topical vasoconstrictors have potential adverse effects; therefore, the property of each agent should be considered.
Infiltration of a solution of local anesthetic with vasoconstrictor has been introduced to minimize intraoperative bleeding. Hemostatic efficacy of local anesthetic with vasoconstrictor was demonstrated in a study that showed decreased bleeding when lidocaine/epinephrine was injected as compared to injection of placebo (
Arterial pressure and heart rate were affected immediately after injection of lidocaine/epinephrine but were not elevated over the normal range [
Low-flow bleeding (capillary, venous, and small arteries) can be inhibited by the topical application of absorbable biomaterials. Recent development of numerous biomaterials has provided new methods for effective intraoperative and postoperative hemostasis, while avoiding complications, such as adhesions, excessive granulation tissue, and crusting.
Topical antifibrinolytics (i.e., epsilon-aminocaproic acid, tranexamic acid) mechanism of action is competitive binding with the lysine site on plasminogen. This prevents fibrinolysis and stabilizes the blood clot potentially decreasing further bleeding. However, the epsilon-aminocaproic acid was demonstrated to be ineffective in reducing intraoperative bleeding. Conversely, a low dose (100 mg) of tranexamic acid provided hemostasis and improved quality of the surgical field at 2, 4, and 6 minutes after application (
Topical matrix sealant consists of human thrombin and gelatin matrix granules of bovine or porcine gelatin. It provides tamponade of injured vessels and rapid clot formation on the tissue surface. Topical gelatin-thrombin matrixes have been modified to allow their use during endoscopic skull base endonasal surgery. It stops bleeding on an average of 2 minutes (range 1–5 minutes) after its application [
A prospective one-arm study evaluated the efficacy and complications associated with porcine gelatin. Hemostasis was achieved within 10 minutes after application. No serious adverse effects, such as synechiae, adhesions, or infections, were encountered [
Microporous polysaccharide hemispheres are a novel hemostatic biomaterial agent produced from purified potato starch that acts to dehydrate blood and concentrate bloody components, including platelets, red blood cells, and clotting factors. One study demonstrated its hemostatic effect at approximately 30 to 45 seconds and no significant break-through bleeding in 5 minutes after application [
Other biomaterial agents such as oxidized methylcellulose [
Hot water irrigation was originally introduced as a treatment of epistaxis [
Sinonasal and skull base tumors, especially vascular tumors, are challenging for endoscopic skull base surgeons. One principle for the resection of vascular tumors is that of early control of the feeding vessels [
Visualization of the surgical field (making the anatomy more discernible) is greatly enhanced by preventing bleeding. Gentle manipulation is required for resection of tumors, especially those that are intradural, where the technique includes sequential subcapsular debulking, extracapsular sharp dissection, and gradual countertraction using meticulous and light suctioning. Avulsion of tumor tissue should be avoided as it may injure adjacent vital structures. In addition, adequate visualization of dissection planes, avoiding blind instrumentation, and avoiding direct or indirect injury from powered instruments (e.g., drills, microdebriders, and ultrasonic aspirators) are fundamental [
Numerous strategies are available to minimize intraoperative bleeding and improve the endoscopic surgical field. Regardless, anesthetic techniques (controlled hypotension, anesthetic agents) and surgical techniques (surgical techniques, topical vasoconstrictor, and hemostatic biomaterials) enhance the ability of each other to control bleeding. Therefore, cooperation between the anesthetic and surgical teams is of utmost importance to apply the appropriate techniques on each patient.
High-frequency jet ventilation
Laryngeal mask airway
Nonsteroidal anti-inflammatory drugs
International normalized ratio
Low-molecular-weight heparin
n-Butylcyanoacrylate
Ethyl-vinyl alcohol copolymer
End tidal carbon dioxide
Intermittent positive pressure ventilation
Gamma-aminobutyric acid
N-methyl d-aspartate
Angiotensin-converting enzyme
Total intravenous anesthesia
Glomerular filtration rate
Mean arterial pressure
Minimum alveolar concentration
Cyclic guanosine monophosphate.
All authors have no personal financial or institutional interest in any of the materials and devices described in this article. The authors identified no conflict of interests.