Complications of Transsphenoidal Surgery - Discussion
Complications related to indications
Complications resulting from transsphenoidal surgery can be traced to a number of causes, including improper indications, a variety of intercurrent medical conditions, anesthesia, the anatomy surrounding the approach and pituitary, the endocrine systems involved, and, clearly, the surgical technique. The transsphenoidal approach is indicated for pituitary microadenomas, enclosed macroadenomas with predominantly symmetrical suprasellar extension, and some invasive pituitary tumors (principally into the sphenoid bone and clivus) (12, 26, 33, 36, 50, 61, 68, 71, 74,77, 89, 94, 99). Saito et al. (83) suggested staged transsphenoidal removal of pituitary adenomas when the suprasellar extension is greater than 30 mm. The presence of a significant asymmetric suprasellar adenoma extension and of a constrictive diaphragma sellae may constitute a relative contraindication for the transsphenoidal approach, unless the magnetic resonance imaging results suggest a soft tumor consistency, hemorrhage into the tumor, or cyst formation (14, 66, 72, 87, 97). Adenomas with large and complex suprasellar extensions may require a two stage or simultaneous transcranial-transsphenoidal removal (7).Cavernous sinus invasion by a pituitary adenoma does not constitute a contraindication for the transsphenoidal approach,except when the epicenter of the tumor is lateral to the carotid artery (2, 16, 25, 46, 78). Non-adenomatous lesions involving the sella or the sphenoid bone can also be approached transsphenoidally. However, a normal-sized sella is generally considered a contraindication for the transsphenoidal approach to any suprasellar lesion (Fig. 1) (13, 49, 72). The transsphenoidal approach is also contraindicated in patients with sphenoid sinusitis and intrasellar vascular anomalies (34,54,58,72,81,96).
Anesthetic and perioperative general medical complications
Anesthetic complications associated with the transsphenoidal operative technique are relatively rare (65). Only one-tenth of the respondents in the national survey reported having witnessed an anesthetic complication. The transsphenoidal procedure is usually well tolerated by the elderly and by those with medical conditions such as cardiac or pulmonary disease or diabetes, as long as their functional and endocrine status has been evaluated by appropriate preoperative studies (53). Although a detailed analysis of all possible medical and anesthetic complications is beyond the scope of this article, note should be made of growth hormone-related cardiomyopathy in acromegalic patients (59).Preoperative treatment with somatostatin analogues is usually associated with remarkable improvement of the cardiomyopathy. Acromegalic patients are also more prone to having airway and postintubation difficulties. Because of these difficulties, they should remain intubated until they are fully awake after surgery(28, 64,100).
Finally, deep-vein thrombosis and pulmonary emboli have been reported to occur with relative frequency after transsphenoidal surgery (8, 72, 99, 101). The two operative deaths in our series occurred as a consequence of pulmonary emboli. Deep-vein thrombosis prophylaxis should therefore be a part of the surgical strategy and perioperative management for all patients undergoing transsphenoidal surgery.
Use of a sublabial incision and removal of the maxillary spine, which becomes necessary when it is very prominent, as in acromegalics, can result in anesthesia of the upper lip and anterior maxillary teeth (57, 67, 93). The decreased sensation, however, is temporary in more than 90% of patients (57, 67). We have not observed a case of columellar retraction as a result of maxillary spine removal (86). Removal of the cartilaginous septum, especially of its superior part, can result in a saddle nose (23, 44, 47, 54, 67).
According to the national survey, nasal septum perforation was observed by one-third of surgeons; it occurred more frequently with the least experienced surgeons (7.6 versus 3.3% in the most experienced group). The incidence of this complication in the literature ranges from 0.3 to 3% (52, 72, 99), with two authors reporting incidences of 7 and 40% (44, 67). A nasal septum perforation tends to occur more often during subsequent transsphenoidal operations (56). Prevention of a septum perforation requires familiarity with the nasal anatomy. In addition, the integrity of the nasal mucosa can be safeguarded by several technical maneuvers. These include submucous injection of a local anesthetic that helps elevate the nasal mucosal sac off the septum, creation of a superior-inferior submucous tunnel on one side of the septum before these tunnels are connected, formation of a posterior submucous tunnel on the opposite side,and dislocation of the nasal cartilage toward the opposite side as a single mucoperichondrial flap (Fig. 2) (51, 52, 67, 94). These maneuvers are designed to prevent formation of opposing bi mucosal tears, the occurrence of which increases the possibility of a permanent postoperative septal defect.
The importance of midline and verticalorientation during dissection toward the sphenoid sinus has been emphasized in the past (34-36, 72). An undue superior dissection can cause anosmia (44, 92) and can injure the cribriform plate and cause a CSF leak(54). Vertical orientation is best achieved with televised fluoroscopy (30, 36, 52). The placement and opening of a bivalve speculum can be complicated, especially in the elderly, by a diastasis of the maxilla (29, 56)or, even worse, by a fracture of the orbit that can potentiallyresult in blindness (Fig. 3) (6, 45, 54, 70, 72).
Postoperative sinusitis can also be considered an approach complication. In the national survey, this complication occurred with an incidence of 8.5%. Two series reported incidences of sinusitis of 15 and 9% (44, 61); the frequency ranged from 1 to 4%in most other series (8, 26, 82, 97). Earlier removal of the nasal packing and routine use of an oral antibiotic for 7 to 10 days postoperatively can reduce the incidence of this complication.
In the process of opening the sphenoid rostrum, bleeding can occur from the mucosal branch of the sphenopalatine artery. This artery can be the source of delayed postoperative epistaxis (8,14, 82, 99, 101). Ligation or embolization of the internal maxillary artery may become necessary if the epistaxis persists or recurs. The estimated percentage of operations resulting in this complication in the national survey ranged from 0.4 to 4.3% in the three experience groups.
If the speculum is advanced too far interiorly into the sphenoid sinus, a fracture of the sphenoid body can occur, with the possibility of injuring the optic nerves and carotid arteries(6, 54). The inferior medial wall of the optic nerve canals protrudes into the superior lateral extent of the sphenoid sinus. The bony plate shielding the optic nerves can be extremely thin or it may be completely missing (81, 92). It is not surprising,therefore, that the optic nerves in this location are vulnerable not only to surgical manipulations but also to heat injury. Consequently, the use of monopolar coagulation should be avoided inside the sphenoid sinus. In addition, the bone over the anterior loop of the carotid artery that protrudes into the sphenoid sinus on either side of the anterior inferior walls of the sella is missing in approximately 4% of cadaveric specimens, with the sphenoid sinus mucosa directly abutting the adventitia of the artery (56, 81, 86). This anatomic variant must be kept in mind in the process of removing the sphenoid sinus mucosa, a maneuver considered necessary by most neurosurgeons as a means of preventing formation of a sphenoid sinus mucocele (54, 72). In addition to midline orientation, vertical orientation should be carefully maintained in the sphenoid sinus and during opening of the sella, to avoid a too-high trajectory toward the planum or a too-low trajectory toward the clivus, which may be eroded or even missing in patients with destructive tumors (34).
Operative manipulations in the sella can be associated with vascular injuries of the carotid artery in the cavernous sinuses.Death with such injuries has been reported (57, 72, 101). In the national survey, 114 surgeons reported having caused carotid artery injury. The percentage of transsphenoidal operations resulting in carotid artery injuries varied from 0.4% for the most experienced group to 1.4% for the least experienced surgeons, with the difference being statistically significant. The review of the literature revealed 35 additional cases of vascular injuries.Twenty-one of these cases resulted either in false or mycotic aneurysms (3, 10, 52, 72, 73, 79, 99, 101) or in carotid cavernous fistulas (3, 52, 60, 75, 76, 80, 89, 101). Furthermore, cases of postoperative vasospasm and of vascular occlusion (40, 52, 54, 72)have also been reported. A thorough preoperative assessment of the carotid artery position should be obtained and carefully studied in each case (3, 78). The carotid arteries can be found inside the sella (36, 54), and the distance between the two arteries is as short as 4 mm in some patients (57, 81). T1-weighted, infused magnetic resonance imaging of the sella and the pituitary can be relied on in most cases to delineate the anatomic relationships of the carotid artery. Magnetic resonance angiography or digital subtraction angiography may be indicated for patients in whom either a carotid artery anomaly or an aneurysm in the cavernous sinus or in the sella is suspected (96). If torrential hemorrhaging occurs during surgery, packing is virtually all one can do at that time. If the bleeding is controlled, postoperative angiography is imperative; if results are negative, angiography should be repeated after the packing is removed (3). If packing fails to control the bleeding, intraoperative endovascular occlusion of the carotid artery may become necessary. Endovascular occlusion and trapping are also the treatments of choice for false aneurysms and carotid cavernous fistulas (3, 9).
Although it is sometimes necessary to trace pituitary tumors into the medial compartments of the cavernous sinuses (16), this surgical maneuver can also result in an injury to one of the cranial nerves in the cavernous sinus, most often the VIth cranial nerve (14). In the national survey, injuries to the cranial nerves in the cavernous sinus occurred with an incidence of 0.4% for the most experienced group and 1.9% for the least experienced surgeons, with the difference being statistically significant. The reported incidence of this complication in the literature ranges from 0 to 1.2% (15, 25, 52, 56, 72, 99, 101).
Complications resulting from surgical maneuvers in the suprasellar space
Pituitary adenomas originat e below the diaphragma sellae and thus outside the arachnoid membrane and the subarachnoid space (Fig.4). As they grow larger and begin to reach the suprasellar space,they distend the dura ring of the diaphragma and displace the arachnoid membrane (Fig. 5). Consequently, pituitary adenomas, regardless of their size and shape and the direction of their suprasellar extension, remain confined to the extra-arachnoid space (Fig. 6). The displaced and elevated arachnoid membrane constitutes a distinct dissection plane along which even large and sprawling pituitary tumors can be removed completely or at least in gross total fashion (Fig. 7). That the transsphenoidal removal of a pituitary tumor can be performed entirely outside the arachnoid membrane, and thus without entering the subarachnoid space, is the fundamental reason for the benignity of this procedure. A violation of the arachnoid membrane, however, can occur in several circumstances. For example, the arachnoid membrane can be opened and the subarachnoid space entered in a patient with a low-lying anterior arachnoid recess, in the process of opening the dura and during operative maneuvers in the anterior-superior aspect of the sella exposure (14, 57).Furthermore, the arachnoid membrane can be injured in the process of removing a pituitary macroadenoma when the distended and elevated arachnoid membrane over the tumor dome begins to invert into the sella (Fig. 8) (14). Immediate recognition of this intraoperative event is essential to avoid penetration into the subarachnoid space. In most macroadenomas, there is an additional protective thin layer of residual normal anterior pituitary tissue attached to the under surface of the arachnoid membrane.
The incidence of CSF fistulas in the national s urvey ranged from 1.5% for the most experienced surgeons to 4.2% for the least experienced group. The incidence of this complication reported in the literature has been as high as 9 to 15% (42, 44, 82), although most authors describe an incidence between 1 and 4% (8,14, 26, 52,56, 61, 71, 72, 77, 97,101). Failure to close a CSF fistula primarily or repair it secondarily can result in either a tension pneumocephalus (4, 11,14, 72) or meningitis. Most authors report meningitis as occurring with a relatively low incidence, ranging from 0 to 2% (8, 14, 44, 77, 97, 101), although it can result in death (52).
The techniques of sella closure have been described in the literature (17, 35, 51, 52, 77, 90, 94, 99). Our technique has been to use an autologous fascia and fat graft along with an autologous fibrin glue to seal macroscopic openings in the arachnoid membrane. If there is no evidence of an intraoperative CSF leak, a fat graft admixed with pulverized Surgicel is used alone to pack the sella. Care is taken, however, not to pack the sella in a way that would result in an elevation of the arachnoid membrane above the anterior clinoids or cause a compression of the cavernous sinuses. A graft fashioned from a segment of the removed vomer, or in rare instances from a portion of the nasal or rib cartilages, is used to hold the pack in place, with placement as precise as possible between the dura and bony openings of the sella. Spinal drainage is used as the first treatment step in a patient with a persistent CSF fistula and then by re-exploration and repacking if so indicated.
Penetration of the arachnoid membrane can also result in an injury to the intra-arachnoid neuro vascular structures, including the hypothalamus, the optic nerves and chiasm, and the surrounding vessels. In two detailed reviews of complications of transsphenoidal surgery, hypothalamic injuries have been reported as the principal cause of operative death (51, 72,101). In the national survey, 83 surgeons reported having caused a central nervous system injury. Visual loss can be another complication of penetration through the arachnoid membrane. In the nationa lsurvey, 179 surgeons reported having had patients with a postoperative visual loss. The percentage of operations resulting in this complication was 0.4% for the most experienced group and 2.4% for the least experienced group of surgeons, with the difference again being statistically significant. Review of the literature shows that the incidence of visual deterioration after transsphenoidal surgery ranges from 0.6 to 1.6% (6,14, 52, 61, 77,82, 99,101). The mechanism of visual loss can be either direct trauma or vascular compromise and insufficiency (1, 8). The potential for an injury to the optic nerves, chiasm, and hypothalamus is greater in patients undergoing transsphenoidal surgery for recurrent pituitary tumors (55), especially if they were previously operated on transcranially.
With the transcranial approach to a pituitary tumor, the arachnoid membrane is opened before the tumor can be reached. This maneuver thus results in adhesions between the residual sella contents or tumor on one side and the optic apparatus and the hypothalamus on the other. Thus, subsequent transsphenoidal surgery and intrasellar maneuvers can potentially result in a traction injury, contusion, or vascular insufficiency of the optic nerves and chiasm (Fig. 9). It has been our practice, therefore,not to recommend the transsphenoidal approach for patients with large recurrent pituitary tumors previously operated on transcranially. Visual loss can also occur as a consequence of optic nerve and chiasm prolapse into an empty sella months or years after removal of a pituitary macroadenoma (41, 54). Chiasmapexy (20), however, rarely becomes necessary, because the loss of vision is frequently vague and non-progressive.
Surgical manipulations during removal of the suprasellar portion of the tumor, especially if associated with in adequate removal and decompression of the tumor, can cause hemorrhage and swelling in the residual tumor tissue, resulting in death, visual impairment, hydrocephalus, lethargy, or paresis (Fig. 10) (8,14,21, 44, 72, 99,101). The treatment depends on the severity and progression of symptoms and therefore varies from mere observation to the use of cortico steroids, placement of a ventriculoperitoneal shunt, or re-exploration. These complications are more likely to occur in a patient with a constrictive diaphragma sellae and a dumbbell-shaped tumor (74), especially if the tumor contains numerous fibrous septi (14). Suprasellar tumor manipulations have also been reported to be associated with subarachnoid hemorrhage from aneurysmal or non-aneurysmal causes (54, 56, 62, 91),bilateral frontal epidural hematomas (84), and temporal lobe epilepsy (44, 99, 101).
DI and anterior pituitary insufficiency were the most frequent complications reported in the national survey. With the least experienced surgeons, one of five transsphenoidal operations resulted in both of these complications. In contrast, the incidence of these complications was lower in the hands of the most experienced surgeons.
Postoperative anterior pituitary insufficiency has been reported in the literature as being rare (72). Various series cite an incidence ranging from less than 1 to 10% (63, 97,101), with one series reporting an incidence of 27% (82). Postoperative anterior pituitary insufficiency was also reported to occur more frequently after removal of larger tumors and in patients whose anterior pituitary functions were impaired pre-operatively (63).The residual normal anterior pituitary tissue can be identified in the preoperative, T1-weighted, infused magnetic resonance imaging scans as a thin layer of enhanced tissue draping around the tumor,mostly over the upper pole of the tumor (Fig. 11). Every effort should be made to preserve this attenuated, residual, normal anterior pituitary tissue, because it can prove sufficient to maintain or even improve anterior pituitary functions in the postoperative period (64).
Temporary post-transsphenoidal surgery DI has been reported to occur in 10 to 60% of cases (26, 68, 82). Permanent DI, however,seems to be relatively rare, with the reported incidence ranging in most large series from 0.5 to 15% (8, 26, 44, 52, 61, 68, 71,97,101). DI after removal of microadenomas usually occurs as a consequence of stalk manipulations. Vertically oriented vessels on the pale-reddish stalk are helpful landmarks for recognizing the stalk. In pituitary macroadenomas, the stalk and the posterior lobe are often not seen because they can be displaced in any direction, flattened, and covered by a fibrous layer. The latter finding explains the relatively low incidence of permanent postoperative DI in patients undergoing removal of pituitary macroadenomas.
In addition, the postoperative course can be complicated by inappropriate secretion of the antidiuretic hormone, which occurs usually on the 6th or 7th postoperative day and thus frequently after the patient has been released from the hospital (5,15,19,95, 97). One of the explanations for this phenomenon is presumed necrosis of a portion of the posterior lobe because of surgical trauma, resulting in a sudden release of the antidiuretic hormone.
A national survey on complications of transsphenoidal surgery was conducted. Among the 1162 neurosurgeons responding to the survey, 958 (82%) reported performing transsphenoidal surgery.Respondents were divided into three experience groups, according to the number of transsphenoidal operations performed. The estimated mortality rate of 0.9% and the mean incidence (from all of the respondents) of complications such as carotid artery injury(1.1%), central nervous system injury (1.3%), loss of vision(1.8%), CSF fistula (3.9%), meningitis (1.5%), nasal septumperforation (6.7%), and other complications suggested that transsphenoidal surgery, although reasonably safe, can be associated with potentially serious complications. In addition,the survey showed that more experienced surgeons witnessed a larger number of complications, most likely because of their greater caseloads and perhaps because of their tendency to operate on more difficult tumors. The estimated incidences of death and morbidity, however, seemed to be higher with less experienced surgeons. This difference was statistically significant. These data were interpreted with caution, because they are based on estimates by the respondents. The complications of transsphenoidal surgery were also reviewed in light of the available literature and our personal experience.
The authors present a national survey on the complications of transsphenoidal surgery. Although this is informative regarding the approximate incidence of these complications, readers must be aware that the respondents to the survey did not necessarily review their experience as the authors did. It may be that the information returned in such a survey is anecdotal. As an example,I find it odd that 41% of the respondents claimed that they had not seen anterior pituitary insufficiency in any of their postoperative patients. Equally odd is that 34% reported that they had never seen a nasal perforation. The authors have pointed out several times that the respondents to such a survey have probably not reviewed their material as the authors have done.
What is very clear, however, is that experience is important.The incidence of complications seems most closely related to the experience of the surgical team. This is extremely important to observe, particularly at a time when patients choices are being threatened by health care managers.
Kalmon D. Post
New York, New York
The authors report valuable, if not completely valid, information regarding the incidence of various complications related to transsphenoidal surgery. The data are useful, because they reflect the observations of 958 surgeons of varying experience. They are of marginal statistical validity, because the numbers are only estimates by the surgeons. Having been one of the questionnaire respondents in the "over 500 operations"group, I can say that my data were from a compulsively kept computer database, but the authors have no quality control on any of the estimates by the respondents.
Overall, I think that the percentages of the various complications are reasonably accurate. It is not surprising that the complication rates are a bit lower for surgeons with greater experience. Fortunately, the incidence of any given complication is low for all groups reporting.
The authors also offer a valuable service to readers by providing a detailed discussion of all of the possible complications of this procedure. Although this is a low-risk procedure overall, it is important for practitioners to appreciate the various complications that can and will be encountered.
William F. Chandler
Ann Arbor, Michigan
This carefully performed review of the complications of transsphenoidal surgery provides an extraordinarily useful database for considering the risks and outcomes of surgery for pituitary tumors and related lesions. It contains careful categorization of the major different types of complications, some serious and some less devastating but all important.
The spectrum of complications of transsphenoidal surgery is clearly related to the technical aspects of the operation and to the basic aspects of pituitary disease. There is fairly solid evidence that for most complications, the incidence rate decreases significantly with increasing experience on the part of the surgeon. That 9% of the respondents stated that patients had experienced anesthetic complications was of great interest; this suggests that anesthesia for transsphenoidal procedures is more than a trivial event and that some aspects of pituitary disease,such as acromegaly, may increase the likelihood of such complications.
Clearly it would have been difficult to gather firm data regarding the incidence of misdirected surgical approaches. This complication does occur even with the best surgeons, and a misdirected approach that guides the surgeon intracranially through the cribriform plate or through the clivus below the sellais a significant hazard. Both aspects of the misdirected approach can, of course, produce both direct brain injury and cerebrospinal fluid (CSF) rhinorrhea.
A few comments regarding the avoidance of complications might be useful for consideration of the data presented here. First,careful anatomic analysis of the preoperative imaging studies is essential and is of great help in maintaining the midline approach. The preservation of midline structures whenever possible and the ability to keep them in view until the sella is open provide a great deal of safety and are, of course, confirmed in the lateral view with x-ray control. Meticulous surgical technique with careful hemostatis is also critical in preventing the obscuring of important anatomic details. Diabetes insipidus can best be precluded by avoiding manipulation of the pituitary stalk when operating on intrasellar tumors wherein the posterior pituitary and the pituitary stalk might be observed or traumatized. Preservation of the normal pituitary gland depends on the ability of the surgeon to recognize the sometimes membranous remnants of the normal pituitary and to preserve them carefully while thoroughly removing the tumor. It is our preference to use tissue packing (abdominal fat) of the tumor cavity or empty sellaonly when there has been a CSF leak (this includes overt CSF leaks and the "weeping" type of CSF leak that may be seen because of an arachnoidal diverticulum within the sella or a very thinned diaphragm). We have not found the addition of either fascia lata or fibrin glue to aid significantly in the security ofthe packing and in the prevention of postoperative CSF leaks. When there has been no CSF leak, it is our preference simply to pack the tumor cavity with Gelfoam. In both cases, careful reconstruction of the floor of the sella is accomplished by using septal cartilage or bone.
When a CSF leak does occur in the postoperative period, we favor immediate re-exploration and repacking. Although we have had a few patients for whom the leak has stopped with prolonged lumbar drainage, it is such a simple process to re-explore fresh transsphenoidal cases that re-exploration and repacking have been almost uniformly successful, avoiding the anxiety of maintaining lumbar drainage for the patients. We also recommend immediate re-exploration for unanticipated visual loss or cranial nerve palsy when the patient awakens after surgery. This usually occurs either because the sella has been packed too tightly or because there has been some hemorrhaging, which can be removed.
Nasal septal perforations can be unpleasant complications inpatients who are otherwise well. They usually occur because the nasal mucous membrane is damaged in similar areas on both sides of the septal cartilage. When this sort of mucosal damage occurs, the surgeon should make every possible attempt to perform a direct repair of the torn mucosa, at least on one side of the nasal septum. Delayed repair of a symptomatic nasal septal perforation can occasionally be accomplished with a silastic button, and we had one case in which a colleague, an ear, nose, and throat specialist, successfully repaired the perforation by using duralgraft material.
It is clear that endocrine complications, such as iatrogenic hypopituitarism and diabetes insipidus, decrease with the experience of the surgeon with transsphenoidal procedures, and this is probably related to gentle technique and careful dissection within the sella itself. It will be interesting to see how the use of endoscopic techniques may alter the incidence and severity of these types of complications.
Carotid artery injuries can always occur. Careful analysis of the magnetic resonance imaging scans before the dura is incised is highly recommended. If the carotid artery is violated, the surgeon must be willing to acknowledge this, to stop the bleeding, and then to perform angiography as soon as possible after the operation. Even if the artery seems to be successfully repaired by packing (direct suture repair is obviously the most desirable management strategy if it can be accomplished), a subsequent angiogram should be planned because the majority of these patients develop false aneurysms and, if this late complication is untreated, the results are frequently catastrophic. Although endovascular techniques are usually successful in dealing with false aneurysms, we had one patient for whom direct repair within the cavernous sinus, through a craniotomy, was necessary.
For most surgical complications, the best strategy is avoidance. This depends on a thorough understanding of the disease, the surgery, and the techniques that need to be used to obtain optimal results.
Edward R. Laws, Jr.
This article presents an excellent overview of the complications that can be associated with transsphenoidal surgery.It is interesting to consider the findings in this perspective,with such a large number of cases presented. I am sure that there are many complications that most neurosurgeons have never encountered and some that occur frequently about which we have perhaps become a little too unconcerned. This is an important compilation of data.
This work was supported by the Department of Surgery, Evanston Hospital, and the Bennett-Tarkington Chair in Neurosurgery, Evanston Hospital and Northwestern University Medical School.
Received: March 18, 1996.
Accepted: August 22, 1996.
Reprint requests: Ivan Ciric, M.D., Division of Neurosurgery, Evanston Hospital, 2650 Ridge Avenue, Evanston, IL 60201.
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