CLINICAL INVESTIGATION
Dexamethasone PONV Prophylaxis Alters the Hypothalamic-Pituitary-Adrenal Axis After Transsphenoidal Pituitary Surgery Till Burkhardt, MD,* Roman Rotermund, MD,* Nils-Ole Schmidt, MD,* Rainer Kiefmann, MD,w and Jo¨rg Flitsch, MD*
Background: Postoperative nausea and vomiting (PONV) is common after general anesthesia and are reported by approximately 20% to 25% of all patients and up to 39% of patients undergoing neurosurgical procedures. The most common standard prophylaxis is a single application of 4 mg of dexamethasone before initiating anesthesia. Dexamethasone is known to suppress adreno-corticotroph hormone and cortisol levels. The objective was to find out whether this prophylaxis has an effect on the postoperative levels of cortisol in patients undergoing transsphenoidal pituitary surgery, and therefore simulates pituitary deficiency. Patients and Methods: A retrospective analysis of the files of 136 consecutive patients who were operated during a course of 6 months were included. Nineteen patients with a known history of PONV received a standard dose of 4 mg of dexamethasone perioperatively. Blood tests were drawn at the first postoperative day and were compared with blood tests of patients who had no history of PONV and therefore received no prophylaxis. Results: Patients who were treated with a dexamethasone PONV prophylaxis showed no significant changes in cortisol levels; preoperative median of 93 mg/L (range, 39 to 427) and a postoperative median of 87 mg/L (range, 10 to 733; P = 0.798) opposed to patients who did not receive such treatment; preoperative cortisol 114 mg/L (range, 10 to 387) and postoperative levels of 273 mg/L (range, 10 to 1352; P < 0.001). Conclusions: As early postoperative blood checks of the cortisol levels yield important information about potential pituitary sufficiency after transsphenoidal surgery, the probability that dexamethasone PONV prophylaxis suppresses postoperative cortisol levels should be considered. Key Words: PONV, pituitary surgery, cortisol, ACTH (J Neurosurg Anesthesiol 2014;26:216–219)
Received for publication April 2, 2013; accepted July 30, 2013. From the Departments of *Neurosurgery; and wAnaesthesiology, University Medical Center, Hamburg-Eppendorf, Germany. The authors have no funding or conflicts of interest to disclose. Reprints: Till Burkhardt, MD, Department of Neurosurgery, University Medical Center, Hamburg-Eppendorf, Martinistrasse 52, 20251 Hamburg, Germany (e-mail: [email protected]). Copyright r 2014 by Lippincott Williams & Wilkins
216 | www.jnsa.com
P
ostoperative nausea and vomiting (PONV) is a common side effect of general anaesthesia and is reported in up to 39% of all patients after neurosurgical procedures.1 The overall rate of PONV is related to numerous factors, for example, patient’s age, sex, type of anesthetic drug, type of surgical procedure, and duration of the surgical procedure.2 The physical act of vomiting may increase intracranial pressure or cerebral intravascular pressure, putting patients at a risk for postoperative hemorrhage and cerebrospinal fluid (CSF) leakage3 Different drugs are available to prevent or lower the incidence of PONV and numerous trials have shown the efficacy of perioperative administration of dexamethasone to prevent PONV after general anesthesia.4 Dexamethasone is known to suppress the production and secretion of adreno-corticotroph hormone (ACTH) and therefore lowers the adrenal cortisol production over a time frame of >24 hours.5 This effect is used in the well-established dexamethasone suppression tests for the diagnosis of Cushing’s syndrome. Early postoperative blood levels of cortisol and ACTH yet again yield very important information in pituitary surgery,6–8 as these levels can indicate either early recovery or loss of pituitary function, for example, after excessive surgery for large pituitary tumors. Most authors recommend early postoperative cortisol measurement after pituitary surgery before substitution of glucocorticoids in case of suspected insufficiency.9 In Cushing’s disease, the early postoperative drop in ACTH and cortisol to subnormal levels predict the remission of the disease. However, the influence of preoperative PONV prophylaxis by dexamethasone on the assessment of disease remission after pituitary surgery by measurement of the postoperative cortisol and ACTH levels are still unclear. Here we investigated the effect of PONV prophylaxis with a standard dose of 4 mg of dexamethasone on early postoperative cortisol levels after surgery for different pituitary lesions.
PATIENTS AND METHODS The data of 136 consecutive patients, who were operated for pituitary tumors at the authors’ department between June 2012 and December 2012, were retrospectively J Neurosurg Anesthesiol
Volume 26, Number 3, July 2014
J Neurosurg Anesthesiol
Volume 26, Number 3, July 2014
analyzed and were screened for a positive history of PONV. This study was in line with the institutional and ethical guidelines of the University Medical Center HamburgEppendorf. All patients gave written, informed consent into the subsequent use of all treatment-related, anonymized data for study purposes, as this is routinely done at our department. The median patient’s age was 51 years (range, 14 to 78 y); there were 68 female and 68 male patients. Pathologies varied from hormone-inactive adenoma in 65 patients, acromegaly in 30 patients, Cushing disease in 19 patients, prolactinomas in 5 patients, and TSHoma in 1 patient. Nonadenomatous pathologies were: meningioma (4 patients), craniopharyngioma (4 patients), colloid cyst (4 patients), and arachnoid cyst, germinoma, hypophysitis, and Rathke cleft cyst (1 patient each). Histopathologic analysis of all specimens was performed by the Department of Neuropathology at the University Medical Center Hamburg-Eppendorf. Owing to the nature of Cushing’s disease with highly elevated cortisol levels and the intent to lower these levels by surgery to subnormal, these cases were excluded from further analysis (n = 19). Anesthetic technique and postoperative management are standardized at our facility. Anesthesia was steered with propofol and remifentanil in all cases. Postoperative management included further observation and treatment of pain and possible PONV in the postanesthesia care unit and subsequent transfer to the patients ward after the patient was reliably conscious and orientated. A standard dose of 4 mg dexamethasone PONV prophylaxis was administered, if patients suffered from PONV after previous surgery. Risk factors for PONV were evaluated, according to Apfel’s simplified score. In 19 patients who reported nausea and vomiting after previous general anesthesia for other medical problems, a dose of 4 mg of dexamethasone was administered shortly before the initiation of narcosis. Early postoperative cortisol and ACTH levels were measured in all patients on postoperative day 1 (08:00 hours) using a commercially available immunoassay (Cobas e411, Roche Diagnostics).
Statistical Analysis
Group 1 Statistical analysis of these patients (n = 98) revealed median preoperative blood levels after admission of cortisol of 114 mg/L (range, 10 to 387 mg/L) and postoperative levels of 273 mg/L (range, 10 to 1352 mg/L). ACTH levels elevated from a median 16 ng/L (range, 5 to 169 ng/L) to 18 ng/L (range, 5 to 112 ng/L) postoperatively. Both hormones elevated in a significant manner with P < 0.001 for changes of cortisol and P = 0.002 for changes of ACTH levels derived from Wilcoxon signed-rank tests (Figs. 1, 2).
Group 2 Patients with a positive history of PONV and dexamethasone prophylaxis (n = 19) showed median preoperative blood levels of 93 mg/L (range, 39 to 427 mg/L) for cortisol, and median levels of 87 mg/L (range, 10 to 733 mg/L) postoperatively. Statistical analysis revealed a nonsignificant change, P = 0.798. Median ACTH levels did not reveal a significant change with 13 ng/L (range, 5 to 37 ng/L) to 14.5 ng/L (range, 5 to 52 ng/L; P = 0.787; Figs. 1, 2).
Duration of Surgery and Time to Next Morning Blood Draw The median duration of surgery was 85 minutes, with a range of 34 to 189 minutes. The time between extubation and next morning blood draws of the patients was a median of 19.5 hours, with a range of 13.4 to 23.25 hours.
PONV Nine patients suffered from nausea and vomiting within the first 24 hours after extubation, of whom 3 had reported PONV after previous surgery and had therefore received 4 mg of dexamethasone. Five patients reported nausea without the urge to vomit after surgery, of whom 3 received 4 mg of dexamethasone as PONV prophylaxis.
CSF Leakage Three patients from group 1 had to undergo a secondary surgery for CSF leakage; one of these patients reported nausea but no vomiting.
DISCUSSION
Wilcoxon signed-rank tests were conducted to evaluate changes between preoperative and postoperative figures; P < 0.05 was considered significant.
RESULTS Cortisol and ACTH levels A total of 117 consecutive patients suffering from pituitary disorders other than Cushing’s disease in this study were divided into 2 groups: group 1 (n = 98) did not report any history of PONV, and therefore did not receive any prophylactic glucocorticoid medication. Group 2 (n = 19) had a positive history of PONV and received a perioperative prophylaxis of 4 mg of dexamethasone. r
Dexamethasone PONV-Prophylaxis and Pituitary Surgery
2014 Lippincott Williams & Wilkins
Dexamethasone is a very potent prophylactic antiemetic and is therefore frequently used during surgical and neurosurgical procedures,4 as PONV may cause potentially dangerous consequences in neurosurgical patients, as elevated blood pressure and elevated intracranial pressure during vomiting may cause hemorrhage and CSF leakage,3 the latter especially after transsphenoidal pituitary surgery. However, dexamethasone suppresses the pituitary-adrenal axis; this effect is used in different diagnostic tests for pituitary disorders and may, if used as a PONV prophylaxis, lead to low postoperative levels of cortisol after pituitary surgery. Therefore, we investigated the effect of dexamethasone as PONV prophylaxis on postoperative levels of ACTH and cortisol. www.jnsa.com |
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Burkhardt et al
FIGURE 1. Box whisker plots of ACTH, preoperative and postoperative for patients with and without perioperative administration of dexamethasone. ACTH indicates adreno-corticotroph hormone; PONV, postoperative nausea and vomiting.
In our series of 117 patients, with 98 patients not receiving dexamethasone (group 1), a postoperative elevation of cortisol levels was observed; this is in line with a typical stress response to surgery. However, a similar response was missing in patients who received dexamethasone (group 2). Although there are limitations to this study, particularly the retrospective design, the limited number of patients receiving PONV prophylaxis, the variety of pituitary pathologies, and the time frame from the end of surgery to the measurement of postoperative ACTH and cortisol levels, the results of this study still clearly demonstrate the suppressive effect of a standard dose of 4 mg of dexamethasone on early postoperative cortisol levels in patients suffering from pathologies other than Cushing’s disease, thus possibly simulating pituitary deficiency and possibly forcing the patient into an unnecessary glucocorticoid substitution.
J Neurosurg Anesthesiol
Volume 26, Number 3, July 2014
In this cohort, we did not find an elevation of CSF leakage after surgery with 3 patients having to undergo revisional surgery, of whom 1 reported nausea (6/10 on the visual analog scale), but no vomiting. Early postoperative blood tests and hormone evaluation after pituitary surgery include key information for the neurosurgeon to assess the success or failure of an operation and complications both in hormone-secreting and inactive adenomas.10,11 Owing to its circadian rhythm and immediate response to changes in pituitary function, the most important marker is cortisol. Undetected secondary adrenal insufficiency after surgery endangers the patient’s life. Normal or even elevated early postoperative cortisol levels almost certainly exclude loss of corticotroph and even further pituitary functions after surgery, although patients with low cortisol levels may need prompt substitution of hydrocortisone.9 As the prophylactic control of PONV does not solely rely on dexamethasone, one should seek alternatives such as ondansetron,12–14 granisetron,15 or droperidol,16 which have also been proven to be efficient antiemetics and have a prophylactic effect on PONV in neurosurgical procedures and patients.17 As these drugs have no influence on the hypothalamic-pituitary-adrenal axis, there should not be any alteration of early postoperative cortisol levels in these patients. If dexamethasone PONV prophylaxis is unavoidable, for example, in cases of known allergies to the above-mentioned alternatives, a close communication between the anesthesiologist and surgeon is of the essence.
CONCLUSIONS The results of this study document the suppression of early postoperative cortisol levels after pituitary surgery as a side effect of dexamethasone used as PONV prophylaxis. The authors therefore recommend drugs other than dexamethasone to treat or prevent PONV in patients undergoing pituitary surgery. REFERENCES
FIGURE 2. Box whisker plots of cortisol, preoperative and postoperative for patients with and without perioperative administration of dexamethasone. PONV indicates postoperative nausea and vomiting.
218 | www.jnsa.com
1. Audibert G, Vial V. Postoperative nausea and vomiting after neurosurgery (infratentorial and supratentorial surgery). Ann Fr Anesth Reanim. 2004;23:422–427. 2. Gan TJ. Risk factors for postoperative nausea and vomiting. Anesth Analg. 2006;102:1884–1898. 3. Habib AS, Keifer JC, Borel CO, et al. A comparison of the combination of aprepitant and dexamethasone versus the combination of ondansetron and dexamethasone for the prevention of postoperative nausea and vomiting in patients undergoing craniotomy. Anesth Analg. 2011;112:813–818. 4. Apfel CC, Korttila K, Abdalla M, et al. The IMPACT Investigators. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med. 2004;350:2441–2451. 5. Jung C, Alford FP, Topliss DJ, et al. The 4-mg intravenous dexamethasone suppression test in the diagnosis of Cushing´s syndrome. Clin Endocrinol (Oxf). 2010;73:78–84. 6. Mclaughlin N, Cohan P, Barnett P, et al. Early morning cortisol levels as predictors of short-term and long-term adrenal function after endonasal transsphenoidal surgery for pituitary adenomas and Rathke’s cleft cysts. World Neurosurg. 2012. doi: 10.1016/ j.wneu.2012.07.034. [Epub ahead of print]. 7. Marko NF, Gonugunta VA, Hamrahian AH, et al. Use of morning serum cortisol level after transsphenoidal resection of pituitary r
2014 Lippincott Williams & Wilkins
J Neurosurg Anesthesiol
8. 9. 10.
11.
12.
r
Volume 26, Number 3, July 2014
adenoma to predict the need for long-term glucocorticoid supplementation. J Neurosurg. 2009;111:540–544. Inder WJ, Hunt PJ. Glucocorticoid replacement in pituitary surgery: guidelines for perioperative assessment and management. J Clin Endocrinol Metab. 2002;87:2745–2750. Flitsch J, Knappe UJ, Lu¨decke DK. The use of postoperative ACTH levels as a marker for successful transphenoidal microsurgery in Cushing´s disease. Zentralbl Neurochir. 2003;64:6–11. Barkan AL, Blank H, Chandler WF. Pituitary surgery: peri-operative management. In: Swearingen B, Biller BMK, eds. Diagnosis and Management of Pituitary Disorders. Totowa: Humana Press; 2008:303–320. Esposito F, Dusick JR, Cohan P, et al. Clinical review: early morning cortisol levels as a predictor of remission after transsphenoidal surgery for Cushing´s disease. J Clin Endocrinol Metab. 2006;91:7–13. Domino KB, Anderson EA, Polissar NL, et al. Comparative efficacy and safety of ondansetron, droperidol, and metoclopramide for preventing postoperative nausea and vomiting: a meta-analysis. Anesth Analg. 1999;88:1370–1379.
2014 Lippincott Williams & Wilkins
Dexamethasone PONV-Prophylaxis and Pituitary Surgery
13. Figueredo ED, Canosa LG. Ondansetron in the prophylaxis of postoperative vomiting: a meta-analysis. J Clin Anesth. 1998;10: 211–221. 14. Fabling JM, Gan TJ, El-Moalem HE, et al. A randomized, doubleblind comparison of ondansetron versus placebo for prevention of nausea and vomiting after infratentorial craniotomy. J Neurosurg Anesthesiol. 2002;14:102–107. 15. Jain V, Mitra JK, Rath GP, et al. A randomized, doubleblinded comparison of ondansetron, granisetron, and placebo for prevention of postoperative nausea and vomiting after supratentorial craniotomy. J Neurosurg Anesthesiol. 2009;21:226–230. 16. Eberhart LH, Morin AM, Bothner U, et al. Droperidol and 5-HT3-receptor antagonists, alone or in combination, for prophylaxis of postoperative nausea and vomiting. A meta-analysis of randomized controlled trials. Acta Anaesthesiol Scand. 2000;44: 1252–1257. 17. Neufeld SM, Newburn-Cook CV. The efficacy of 5-HT3 receptor antagonists for the prevention of postoperative nausea and vomiting after craniotomy: a meta-analysis. J Neurosurg Anesthesiol. 2007;19: 10–17.
www.jnsa.com |
219
Dexamethasone PONV Prophylaxis Alters the Hypothalamic-Pituitary-Adrenal Axis After Transsphenoidal Pituitary Surgery Till Burkhardt, MD,* Roman Rotermund, MD,* Nils-Ole Schmidt, MD,* Rainer Kiefmann, MD,w and Jo¨rg Flitsch, MD*
Background: Postoperative nausea and vomiting (PONV) is common after general anesthesia and are reported by approximately 20% to 25% of all patients and up to 39% of patients undergoing neurosurgical procedures. The most common standard prophylaxis is a single application of 4 mg of dexamethasone before initiating anesthesia. Dexamethasone is known to suppress adreno-corticotroph hormone and cortisol levels. The objective was to find out whether this prophylaxis has an effect on the postoperative levels of cortisol in patients undergoing transsphenoidal pituitary surgery, and therefore simulates pituitary deficiency. Patients and Methods: A retrospective analysis of the files of 136 consecutive patients who were operated during a course of 6 months were included. Nineteen patients with a known history of PONV received a standard dose of 4 mg of dexamethasone perioperatively. Blood tests were drawn at the first postoperative day and were compared with blood tests of patients who had no history of PONV and therefore received no prophylaxis. Results: Patients who were treated with a dexamethasone PONV prophylaxis showed no significant changes in cortisol levels; preoperative median of 93 mg/L (range, 39 to 427) and a postoperative median of 87 mg/L (range, 10 to 733; P = 0.798) opposed to patients who did not receive such treatment; preoperative cortisol 114 mg/L (range, 10 to 387) and postoperative levels of 273 mg/L (range, 10 to 1352; P < 0.001). Conclusions: As early postoperative blood checks of the cortisol levels yield important information about potential pituitary sufficiency after transsphenoidal surgery, the probability that dexamethasone PONV prophylaxis suppresses postoperative cortisol levels should be considered. Key Words: PONV, pituitary surgery, cortisol, ACTH (J Neurosurg Anesthesiol 2014;26:216–219)
Received for publication April 2, 2013; accepted July 30, 2013. From the Departments of *Neurosurgery; and wAnaesthesiology, University Medical Center, Hamburg-Eppendorf, Germany. The authors have no funding or conflicts of interest to disclose. Reprints: Till Burkhardt, MD, Department of Neurosurgery, University Medical Center, Hamburg-Eppendorf, Martinistrasse 52, 20251 Hamburg, Germany (e-mail: [email protected]). Copyright r 2014 by Lippincott Williams & Wilkins
216 | www.jnsa.com
P
ostoperative nausea and vomiting (PONV) is a common side effect of general anaesthesia and is reported in up to 39% of all patients after neurosurgical procedures.1 The overall rate of PONV is related to numerous factors, for example, patient’s age, sex, type of anesthetic drug, type of surgical procedure, and duration of the surgical procedure.2 The physical act of vomiting may increase intracranial pressure or cerebral intravascular pressure, putting patients at a risk for postoperative hemorrhage and cerebrospinal fluid (CSF) leakage3 Different drugs are available to prevent or lower the incidence of PONV and numerous trials have shown the efficacy of perioperative administration of dexamethasone to prevent PONV after general anesthesia.4 Dexamethasone is known to suppress the production and secretion of adreno-corticotroph hormone (ACTH) and therefore lowers the adrenal cortisol production over a time frame of >24 hours.5 This effect is used in the well-established dexamethasone suppression tests for the diagnosis of Cushing’s syndrome. Early postoperative blood levels of cortisol and ACTH yet again yield very important information in pituitary surgery,6–8 as these levels can indicate either early recovery or loss of pituitary function, for example, after excessive surgery for large pituitary tumors. Most authors recommend early postoperative cortisol measurement after pituitary surgery before substitution of glucocorticoids in case of suspected insufficiency.9 In Cushing’s disease, the early postoperative drop in ACTH and cortisol to subnormal levels predict the remission of the disease. However, the influence of preoperative PONV prophylaxis by dexamethasone on the assessment of disease remission after pituitary surgery by measurement of the postoperative cortisol and ACTH levels are still unclear. Here we investigated the effect of PONV prophylaxis with a standard dose of 4 mg of dexamethasone on early postoperative cortisol levels after surgery for different pituitary lesions.
PATIENTS AND METHODS The data of 136 consecutive patients, who were operated for pituitary tumors at the authors’ department between June 2012 and December 2012, were retrospectively J Neurosurg Anesthesiol
Volume 26, Number 3, July 2014
J Neurosurg Anesthesiol
Volume 26, Number 3, July 2014
analyzed and were screened for a positive history of PONV. This study was in line with the institutional and ethical guidelines of the University Medical Center HamburgEppendorf. All patients gave written, informed consent into the subsequent use of all treatment-related, anonymized data for study purposes, as this is routinely done at our department. The median patient’s age was 51 years (range, 14 to 78 y); there were 68 female and 68 male patients. Pathologies varied from hormone-inactive adenoma in 65 patients, acromegaly in 30 patients, Cushing disease in 19 patients, prolactinomas in 5 patients, and TSHoma in 1 patient. Nonadenomatous pathologies were: meningioma (4 patients), craniopharyngioma (4 patients), colloid cyst (4 patients), and arachnoid cyst, germinoma, hypophysitis, and Rathke cleft cyst (1 patient each). Histopathologic analysis of all specimens was performed by the Department of Neuropathology at the University Medical Center Hamburg-Eppendorf. Owing to the nature of Cushing’s disease with highly elevated cortisol levels and the intent to lower these levels by surgery to subnormal, these cases were excluded from further analysis (n = 19). Anesthetic technique and postoperative management are standardized at our facility. Anesthesia was steered with propofol and remifentanil in all cases. Postoperative management included further observation and treatment of pain and possible PONV in the postanesthesia care unit and subsequent transfer to the patients ward after the patient was reliably conscious and orientated. A standard dose of 4 mg dexamethasone PONV prophylaxis was administered, if patients suffered from PONV after previous surgery. Risk factors for PONV were evaluated, according to Apfel’s simplified score. In 19 patients who reported nausea and vomiting after previous general anesthesia for other medical problems, a dose of 4 mg of dexamethasone was administered shortly before the initiation of narcosis. Early postoperative cortisol and ACTH levels were measured in all patients on postoperative day 1 (08:00 hours) using a commercially available immunoassay (Cobas e411, Roche Diagnostics).
Statistical Analysis
Group 1 Statistical analysis of these patients (n = 98) revealed median preoperative blood levels after admission of cortisol of 114 mg/L (range, 10 to 387 mg/L) and postoperative levels of 273 mg/L (range, 10 to 1352 mg/L). ACTH levels elevated from a median 16 ng/L (range, 5 to 169 ng/L) to 18 ng/L (range, 5 to 112 ng/L) postoperatively. Both hormones elevated in a significant manner with P < 0.001 for changes of cortisol and P = 0.002 for changes of ACTH levels derived from Wilcoxon signed-rank tests (Figs. 1, 2).
Group 2 Patients with a positive history of PONV and dexamethasone prophylaxis (n = 19) showed median preoperative blood levels of 93 mg/L (range, 39 to 427 mg/L) for cortisol, and median levels of 87 mg/L (range, 10 to 733 mg/L) postoperatively. Statistical analysis revealed a nonsignificant change, P = 0.798. Median ACTH levels did not reveal a significant change with 13 ng/L (range, 5 to 37 ng/L) to 14.5 ng/L (range, 5 to 52 ng/L; P = 0.787; Figs. 1, 2).
Duration of Surgery and Time to Next Morning Blood Draw The median duration of surgery was 85 minutes, with a range of 34 to 189 minutes. The time between extubation and next morning blood draws of the patients was a median of 19.5 hours, with a range of 13.4 to 23.25 hours.
PONV Nine patients suffered from nausea and vomiting within the first 24 hours after extubation, of whom 3 had reported PONV after previous surgery and had therefore received 4 mg of dexamethasone. Five patients reported nausea without the urge to vomit after surgery, of whom 3 received 4 mg of dexamethasone as PONV prophylaxis.
CSF Leakage Three patients from group 1 had to undergo a secondary surgery for CSF leakage; one of these patients reported nausea but no vomiting.
DISCUSSION
Wilcoxon signed-rank tests were conducted to evaluate changes between preoperative and postoperative figures; P < 0.05 was considered significant.
RESULTS Cortisol and ACTH levels A total of 117 consecutive patients suffering from pituitary disorders other than Cushing’s disease in this study were divided into 2 groups: group 1 (n = 98) did not report any history of PONV, and therefore did not receive any prophylactic glucocorticoid medication. Group 2 (n = 19) had a positive history of PONV and received a perioperative prophylaxis of 4 mg of dexamethasone. r
Dexamethasone PONV-Prophylaxis and Pituitary Surgery
2014 Lippincott Williams & Wilkins
Dexamethasone is a very potent prophylactic antiemetic and is therefore frequently used during surgical and neurosurgical procedures,4 as PONV may cause potentially dangerous consequences in neurosurgical patients, as elevated blood pressure and elevated intracranial pressure during vomiting may cause hemorrhage and CSF leakage,3 the latter especially after transsphenoidal pituitary surgery. However, dexamethasone suppresses the pituitary-adrenal axis; this effect is used in different diagnostic tests for pituitary disorders and may, if used as a PONV prophylaxis, lead to low postoperative levels of cortisol after pituitary surgery. Therefore, we investigated the effect of dexamethasone as PONV prophylaxis on postoperative levels of ACTH and cortisol. www.jnsa.com |
217
Burkhardt et al
FIGURE 1. Box whisker plots of ACTH, preoperative and postoperative for patients with and without perioperative administration of dexamethasone. ACTH indicates adreno-corticotroph hormone; PONV, postoperative nausea and vomiting.
In our series of 117 patients, with 98 patients not receiving dexamethasone (group 1), a postoperative elevation of cortisol levels was observed; this is in line with a typical stress response to surgery. However, a similar response was missing in patients who received dexamethasone (group 2). Although there are limitations to this study, particularly the retrospective design, the limited number of patients receiving PONV prophylaxis, the variety of pituitary pathologies, and the time frame from the end of surgery to the measurement of postoperative ACTH and cortisol levels, the results of this study still clearly demonstrate the suppressive effect of a standard dose of 4 mg of dexamethasone on early postoperative cortisol levels in patients suffering from pathologies other than Cushing’s disease, thus possibly simulating pituitary deficiency and possibly forcing the patient into an unnecessary glucocorticoid substitution.
J Neurosurg Anesthesiol
Volume 26, Number 3, July 2014
In this cohort, we did not find an elevation of CSF leakage after surgery with 3 patients having to undergo revisional surgery, of whom 1 reported nausea (6/10 on the visual analog scale), but no vomiting. Early postoperative blood tests and hormone evaluation after pituitary surgery include key information for the neurosurgeon to assess the success or failure of an operation and complications both in hormone-secreting and inactive adenomas.10,11 Owing to its circadian rhythm and immediate response to changes in pituitary function, the most important marker is cortisol. Undetected secondary adrenal insufficiency after surgery endangers the patient’s life. Normal or even elevated early postoperative cortisol levels almost certainly exclude loss of corticotroph and even further pituitary functions after surgery, although patients with low cortisol levels may need prompt substitution of hydrocortisone.9 As the prophylactic control of PONV does not solely rely on dexamethasone, one should seek alternatives such as ondansetron,12–14 granisetron,15 or droperidol,16 which have also been proven to be efficient antiemetics and have a prophylactic effect on PONV in neurosurgical procedures and patients.17 As these drugs have no influence on the hypothalamic-pituitary-adrenal axis, there should not be any alteration of early postoperative cortisol levels in these patients. If dexamethasone PONV prophylaxis is unavoidable, for example, in cases of known allergies to the above-mentioned alternatives, a close communication between the anesthesiologist and surgeon is of the essence.
CONCLUSIONS The results of this study document the suppression of early postoperative cortisol levels after pituitary surgery as a side effect of dexamethasone used as PONV prophylaxis. The authors therefore recommend drugs other than dexamethasone to treat or prevent PONV in patients undergoing pituitary surgery. REFERENCES
FIGURE 2. Box whisker plots of cortisol, preoperative and postoperative for patients with and without perioperative administration of dexamethasone. PONV indicates postoperative nausea and vomiting.
218 | www.jnsa.com
1. Audibert G, Vial V. Postoperative nausea and vomiting after neurosurgery (infratentorial and supratentorial surgery). Ann Fr Anesth Reanim. 2004;23:422–427. 2. Gan TJ. Risk factors for postoperative nausea and vomiting. Anesth Analg. 2006;102:1884–1898. 3. Habib AS, Keifer JC, Borel CO, et al. A comparison of the combination of aprepitant and dexamethasone versus the combination of ondansetron and dexamethasone for the prevention of postoperative nausea and vomiting in patients undergoing craniotomy. Anesth Analg. 2011;112:813–818. 4. Apfel CC, Korttila K, Abdalla M, et al. The IMPACT Investigators. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med. 2004;350:2441–2451. 5. Jung C, Alford FP, Topliss DJ, et al. The 4-mg intravenous dexamethasone suppression test in the diagnosis of Cushing´s syndrome. Clin Endocrinol (Oxf). 2010;73:78–84. 6. Mclaughlin N, Cohan P, Barnett P, et al. Early morning cortisol levels as predictors of short-term and long-term adrenal function after endonasal transsphenoidal surgery for pituitary adenomas and Rathke’s cleft cysts. World Neurosurg. 2012. doi: 10.1016/ j.wneu.2012.07.034. [Epub ahead of print]. 7. Marko NF, Gonugunta VA, Hamrahian AH, et al. Use of morning serum cortisol level after transsphenoidal resection of pituitary r
2014 Lippincott Williams & Wilkins
J Neurosurg Anesthesiol
8. 9. 10.
11.
12.
r
Volume 26, Number 3, July 2014
adenoma to predict the need for long-term glucocorticoid supplementation. J Neurosurg. 2009;111:540–544. Inder WJ, Hunt PJ. Glucocorticoid replacement in pituitary surgery: guidelines for perioperative assessment and management. J Clin Endocrinol Metab. 2002;87:2745–2750. Flitsch J, Knappe UJ, Lu¨decke DK. The use of postoperative ACTH levels as a marker for successful transphenoidal microsurgery in Cushing´s disease. Zentralbl Neurochir. 2003;64:6–11. Barkan AL, Blank H, Chandler WF. Pituitary surgery: peri-operative management. In: Swearingen B, Biller BMK, eds. Diagnosis and Management of Pituitary Disorders. Totowa: Humana Press; 2008:303–320. Esposito F, Dusick JR, Cohan P, et al. Clinical review: early morning cortisol levels as a predictor of remission after transsphenoidal surgery for Cushing´s disease. J Clin Endocrinol Metab. 2006;91:7–13. Domino KB, Anderson EA, Polissar NL, et al. Comparative efficacy and safety of ondansetron, droperidol, and metoclopramide for preventing postoperative nausea and vomiting: a meta-analysis. Anesth Analg. 1999;88:1370–1379.
2014 Lippincott Williams & Wilkins
Dexamethasone PONV-Prophylaxis and Pituitary Surgery
13. Figueredo ED, Canosa LG. Ondansetron in the prophylaxis of postoperative vomiting: a meta-analysis. J Clin Anesth. 1998;10: 211–221. 14. Fabling JM, Gan TJ, El-Moalem HE, et al. A randomized, doubleblind comparison of ondansetron versus placebo for prevention of nausea and vomiting after infratentorial craniotomy. J Neurosurg Anesthesiol. 2002;14:102–107. 15. Jain V, Mitra JK, Rath GP, et al. A randomized, doubleblinded comparison of ondansetron, granisetron, and placebo for prevention of postoperative nausea and vomiting after supratentorial craniotomy. J Neurosurg Anesthesiol. 2009;21:226–230. 16. Eberhart LH, Morin AM, Bothner U, et al. Droperidol and 5-HT3-receptor antagonists, alone or in combination, for prophylaxis of postoperative nausea and vomiting. A meta-analysis of randomized controlled trials. Acta Anaesthesiol Scand. 2000;44: 1252–1257. 17. Neufeld SM, Newburn-Cook CV. The efficacy of 5-HT3 receptor antagonists for the prevention of postoperative nausea and vomiting after craniotomy: a meta-analysis. J Neurosurg Anesthesiol. 2007;19: 10–17.
www.jnsa.com |
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