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Dexamethasone: Not only an effective antiemetic
Acta Anaesthesiologica Taiwanica 49 (2011) 81–82
Contents lists available at SciVerse ScienceDirect
Acta Anaesthesiologica Taiwanica journal homepage: www.e-aat.com
Editorial View
Dexamethasone: Not only an effective antiemetic
As early as 1956, clinical investigators were interested in factors related to postoperative nausea and vomiting (PONV) and began to embark on its assessment.1 Over the last 50 years, hundreds of randomly controlled trials have been published in the investigation of a variety of efficacies of antiemetics believed to have an impact on the incidence of PONV. An optimal antiemetic regiment should be capable of killing PONV and decreasing its incidence without increasing the risk of unacceptable adverse effects. However, most of the currently used antiemetics, including antihistamines, butyrophenones, and dopamine receptor antagonists have been reported to cause occasional undesirable adverse effects, such as excessive sedation, hypotension, dry mouth, dysphoria, hallucinations, and extrapyramidal signs.2 5-HT3 antagonists are effective for preventing and treating PONV in patients undergoing various types of surgery.3 However, the use of prophylactic antiemetic therapy with 5-HT3 antagonists has been criticized for being too expensive.4 Dexamethasone was first reported to be an effective antiemetic regimen in patients undergoing chemotherapy for cancer in 1981.5 The first clinical trial suggesting that dexamethasone might prevent PONV was published in 1993.6 In 2000, Wang et al7 demonstrated that dexamethasone appeared to be most effective in preventing early PONV when administered before rather than after anesthesia. Unlike other antiemetics, dexamethasone has been found to be very effective in the late postoperative period.8 The biological half-life of dexamethasone is 36–72 h9; thus, the late antiemetic efficacy may be pharmacokinetically favorable. Furthermore, dexamethasone could aid the efficacy of other antiemetics.10 A meta-analysis8 has reported that combining dexamethasone with a 5-HT3 antagonist is the most effective prophylactic means currently available for interventing PONV. The adverse events of headache and constipation were mainly related to 5-HT3 antagonist. In this issue of Acta Anaesthesiologica Taiwanica, Ho et al11 in their review article discourse about the findings on dexamethasone as a preventive drug against PONV and its potential adverse effects. They conclude that dexamethasone is generally considered to be an effective and safe antiemetic. According to the review article, most investigative efforts have centered on the acute phase of emesis that occurs within the first 24 h after anesthesia, and significant forward strides have been made with this problem. However, because the safety of anesthesia and surgery has substantially improved over the years, assessing the quality of postoperative recovery has become a booming theme in clinical research. This important component is often not well-controlled concerning the antiemetics that have proved effective for preventing acute emesis.
Postoperative recovery is a complex process. In 2000, Myles et al12 developed a 40-item scoring system (QoR-40) for evaluating the complex and multidimensional process of postoperative recovery. The baseline QoR-40 questionnaire was provided to patients in the preoperative holding area. Five general quality-oflife dimensions are measured within the QoR-40: physical comfort (12 items), emotional state (9 items), physical independence (5 items), psychological support (7 items), and pain (7 items). Each item is graded on a five-point Likert scale, and global scores range from 40 (extremely poor quality of recovery) to 200 (excellent quality of recovery). The QoR-40 has been used and validated for patients undergoing general and ambulatory surgical procedures. In 2007, a systematic review of instruments used to measure patient-based recovery outcomes determined that the QoR-40 was the only assessment tool that fulfilled the criteria of appropriateness, reliability, validity, responsiveness, precision, interpretability, acceptability, and feasibility.13 In the surgical setting, a truly effective antiemetic regimen would be expected to increase a patient’s comfort, to shorten the patient’s stay in the recovery room, and to prevent the patient’s unplanned hospital readmission because of intractable PONV. The effect of corticosteroids on patient recovery after surgery remains controversial. It has been hypothesized that short-term steroid therapy may (1) elevate the mood state by a direct central nervous system effect or through an attenuation of perioperative inflammatory mediator release,14 (2) diminish shivering through the inhibition of the release of vasoconstrictor and pyrogenic cytokines,15 and (3) attenuate the severity of postoperative fatigue.16 Recently, some published investigations used the QoR-40 for evaluating the effect of dexamethasone on patient-perceived quality of postoperative recovery. In April 2011, Murphy et al14 demonstrated that postoperative QoR-40 scores for pain, emotional state, and physical comfort were all improved in patients who had been given low-dose (8 mg) dexamethasone before undergoing outpatient laparoscopic cholecystectomy procedures. These improvements in recovery were translated into reductions in the length of hospital stay. In May 2011, the same research team reported17 that intraoperative administration of 8 mg of dexamethasone to patients undergoing extracorporeal circulation resulted in significantly improved patient-perceived QoR-40 and reductions in the incidence and severity of febrile responses, shivering, and fatigue in the early postoperative period. However, these improvements in recovery had not translated into reduction in the length of either intensive care unit or hospital stay. These clinical findings suggest that dexamethasone increases patient comfort by means of several direct (e.g. effect on nausea/vomiting, shivering, and fatigue) and indirect (e.g. improved restfulness and sleep by decreasing inflammation
1875-4597/$ – see front matter Copyright Ó 2011, Taiwan Society of Anesthesiologists. Published by Elsevier Taiwan LLC. All rights reserved. doi:10.1016/j.aat.2011.08.002
82
and complications) mechanisms.17 In June 2011, De Oliveria et al18 using the QoR-40 evaluated the dose-dependent effects of dexamethasone on patient recovery after ambulatory gynecological surgery. They found that patients given 0.1 mg/kg of dexamethasone had consumed less opioid painkiller, reported less sore throat, muscle pain, confusion, difficulty in falling asleep, and nausea compared with patients given dexamethasone 0.05 mg/kg of dexamethasone or saline. In summary, we believe that dexamethasone is not only an effective antiemetic but also has beneficial effects on several diverse but interrelated symptoms that determine patient comfort resulting in the overall improved QoR-40 scores. However, only patients with a low-risk unacceptable adverse effects were enrolled in most of the clinical trials. The impact of dexamethasone on outcomes in high-risk patients is not known. The review of Ho et al11 on the studies in the space from 2004 to 2011 on evaluating the potential adverse effects after administering antiemetic doses of dexamethasone reveals that the influence of dexamethasone on glycemia is only short lasting. Even in obese patients with impaired glucose tolerance, the hyperglycemic response is more pronounced but not substantially different when dexamethasone is added in antiemetic treatment. Thus, the benefits of administering dexamethasone should be weighed against the potential side effects of hyperglycemia. However, the limited data were likely unable to detect the uncommon adverse events particularly related to steroids (e.g. impaired wound-healing, postoperative infection) in high-risk patients. Additional large-scale investigations should be made to define the benefits and risks of dexamethasone in the surgical setting, as well as to establish the optimal dose of dexamethasone required to improve postoperative recovery. References 1. Knapp MR, Beecher HK. Postanesthetic nausea, vomiting and retching. J Am Med Assoc 1956;160:376–85. 2. Watcha MF, White PF. Postoperative nausea and vomiting: its etiology, treatment, and prevention. Anesthesiology 1992;77:162–84. 3. Kovac AL. Prevention and treatment of postoperative nausea and vomiting. Drugs 2000;59:213–43. 4. White PF, Watcha MF. Are new drugs cost-effective for patients undergoing ambulatory surgery? Anesthesiology 1993;78:2–5. 5. Aapro MS, Alberts DS. Dexamethasone as an antiemetic in patients treated with cisplatin. N Engl J Med 1981;305:520. 6. Baxendale BR, Vater M, Lavery KM. Dexamethasone reduces pain and swelling following extraction of third molar teeth. Anaesthesia 1993;48:961–4.
Editorial View 7. Wang JJ, Ho ST, Tzeng JI, Tang CS. The effect of timing of dexamethasone administration on its efficacy as a prophylactic antiemetic for postoperative nausea and vomiting. Anesth Analg 2000;91:136–9. 8. Henzi I, Walder B, Tramèr MR. Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review. Anesth Analg 2000;90:186–94. 9. Haynes R. Adrenocorticotropic hormone: adrenocortical steroids and their synthetic analogs-inhibitors of the synthesis and actions of adrenocortical hormones. In: Gilman AG, Gilman LS, Rall TW, Murad F, editors. The pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press; 1990. p. 1447–8. 10. Eberhart LH, Morin AM, Georgieff M. Dexamethasone for prophylaxis of postoperative nausea and vomiting. A meta-analysis of randomized controlled studies. Anaesthesist 2000;49:713–20 [in German]. 11. Ho CM, Wu HL, Ho ST, Wang JJ. Dexamethasone prevents postoperative nausea and vomiting: benefit versus risk. Acta Anaesthesiol Taiwan 2011;49:100–4. 12. Myles PS, Weitkamp B, Jones K, Melick J, Hensen S. Validity and reliability of a postoperative quality of recovery score: the QoR-40. Br J Anaesth 2000;84: 11–5. 13. Herrera FJ, Wong J, Chung F. A systematic review of postoperative recovery outcomes measurements after ambulatory surgery. Anesth Analg 2007;105:63–9. 14. Murphy GS, Szokol JW, Greenberg SB, Avram MJ, Vender JS, Nisman M, et al. Preoperative dexamethasone enhances quality of recovery after laparoscopic cholecystectomy: effect on in-hospital and postdischarge recovery outcomes. Anesthesiology 2011;114:882–90. 15. Yared JP, Starr NJ, Hoffmann-Hogg L, Bashour CA, Insler SR, O’Connor M, et al. Dexamethasone decreases the incidence of shivering after cardiac surgery: a randomized, double-blind, placebo-controlled study. Anesth Analg 1998;87: 795–9. 16. Bisgaard T, Klarskov B, Kehlet H, Rosenberg J. Preoperative dexamethasone improves surgical outcome after laparoscopic cholecystectomy: a randomized double-blind placebo-controlled trial. Ann Surg 2003;238:651–60. 17. Murphy GS, Sherwani SS, Szokol JW, Avram MJ, Greenberg SB, Patel KM, et al. Small-dose dexamethasone improves quality of recovery scores after elective cardiac surgery: a randomized, double-blind, placebo-controlled study. J Cardiothorac Vasc Anesth 2011 [Epub ahead of print]. 18. De Oliveira Jr GS, Ahmad S, Fitzgerald PC, Marcus RJ, Altman CS, Panjwani AS, et al. Dose ranging study on the effect of preoperative dexamethasone on postoperative quality of recovery and opioid consumption after ambulatory gynaecological surgery. Br J Anaesth 2011 [Epub ahead of print].
Yi Lee, Associate Professor Department of Anesthesiology, Buddhist Tzu-Chi General Hospital, Buddhist Tzu-Chi University School of Medicine, Hualien, Taiwan, R.O.C. E-mail: [email protected] Jann-Inn Tzeng, Professor and Chairman* Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan, R.O.C. E-mail: [email protected] (J.-I. Tzeng). * Corresponding author.
Contents lists available at SciVerse ScienceDirect
Acta Anaesthesiologica Taiwanica journal homepage: www.e-aat.com
Editorial View
Dexamethasone: Not only an effective antiemetic
As early as 1956, clinical investigators were interested in factors related to postoperative nausea and vomiting (PONV) and began to embark on its assessment.1 Over the last 50 years, hundreds of randomly controlled trials have been published in the investigation of a variety of efficacies of antiemetics believed to have an impact on the incidence of PONV. An optimal antiemetic regiment should be capable of killing PONV and decreasing its incidence without increasing the risk of unacceptable adverse effects. However, most of the currently used antiemetics, including antihistamines, butyrophenones, and dopamine receptor antagonists have been reported to cause occasional undesirable adverse effects, such as excessive sedation, hypotension, dry mouth, dysphoria, hallucinations, and extrapyramidal signs.2 5-HT3 antagonists are effective for preventing and treating PONV in patients undergoing various types of surgery.3 However, the use of prophylactic antiemetic therapy with 5-HT3 antagonists has been criticized for being too expensive.4 Dexamethasone was first reported to be an effective antiemetic regimen in patients undergoing chemotherapy for cancer in 1981.5 The first clinical trial suggesting that dexamethasone might prevent PONV was published in 1993.6 In 2000, Wang et al7 demonstrated that dexamethasone appeared to be most effective in preventing early PONV when administered before rather than after anesthesia. Unlike other antiemetics, dexamethasone has been found to be very effective in the late postoperative period.8 The biological half-life of dexamethasone is 36–72 h9; thus, the late antiemetic efficacy may be pharmacokinetically favorable. Furthermore, dexamethasone could aid the efficacy of other antiemetics.10 A meta-analysis8 has reported that combining dexamethasone with a 5-HT3 antagonist is the most effective prophylactic means currently available for interventing PONV. The adverse events of headache and constipation were mainly related to 5-HT3 antagonist. In this issue of Acta Anaesthesiologica Taiwanica, Ho et al11 in their review article discourse about the findings on dexamethasone as a preventive drug against PONV and its potential adverse effects. They conclude that dexamethasone is generally considered to be an effective and safe antiemetic. According to the review article, most investigative efforts have centered on the acute phase of emesis that occurs within the first 24 h after anesthesia, and significant forward strides have been made with this problem. However, because the safety of anesthesia and surgery has substantially improved over the years, assessing the quality of postoperative recovery has become a booming theme in clinical research. This important component is often not well-controlled concerning the antiemetics that have proved effective for preventing acute emesis.
Postoperative recovery is a complex process. In 2000, Myles et al12 developed a 40-item scoring system (QoR-40) for evaluating the complex and multidimensional process of postoperative recovery. The baseline QoR-40 questionnaire was provided to patients in the preoperative holding area. Five general quality-oflife dimensions are measured within the QoR-40: physical comfort (12 items), emotional state (9 items), physical independence (5 items), psychological support (7 items), and pain (7 items). Each item is graded on a five-point Likert scale, and global scores range from 40 (extremely poor quality of recovery) to 200 (excellent quality of recovery). The QoR-40 has been used and validated for patients undergoing general and ambulatory surgical procedures. In 2007, a systematic review of instruments used to measure patient-based recovery outcomes determined that the QoR-40 was the only assessment tool that fulfilled the criteria of appropriateness, reliability, validity, responsiveness, precision, interpretability, acceptability, and feasibility.13 In the surgical setting, a truly effective antiemetic regimen would be expected to increase a patient’s comfort, to shorten the patient’s stay in the recovery room, and to prevent the patient’s unplanned hospital readmission because of intractable PONV. The effect of corticosteroids on patient recovery after surgery remains controversial. It has been hypothesized that short-term steroid therapy may (1) elevate the mood state by a direct central nervous system effect or through an attenuation of perioperative inflammatory mediator release,14 (2) diminish shivering through the inhibition of the release of vasoconstrictor and pyrogenic cytokines,15 and (3) attenuate the severity of postoperative fatigue.16 Recently, some published investigations used the QoR-40 for evaluating the effect of dexamethasone on patient-perceived quality of postoperative recovery. In April 2011, Murphy et al14 demonstrated that postoperative QoR-40 scores for pain, emotional state, and physical comfort were all improved in patients who had been given low-dose (8 mg) dexamethasone before undergoing outpatient laparoscopic cholecystectomy procedures. These improvements in recovery were translated into reductions in the length of hospital stay. In May 2011, the same research team reported17 that intraoperative administration of 8 mg of dexamethasone to patients undergoing extracorporeal circulation resulted in significantly improved patient-perceived QoR-40 and reductions in the incidence and severity of febrile responses, shivering, and fatigue in the early postoperative period. However, these improvements in recovery had not translated into reduction in the length of either intensive care unit or hospital stay. These clinical findings suggest that dexamethasone increases patient comfort by means of several direct (e.g. effect on nausea/vomiting, shivering, and fatigue) and indirect (e.g. improved restfulness and sleep by decreasing inflammation
1875-4597/$ – see front matter Copyright Ó 2011, Taiwan Society of Anesthesiologists. Published by Elsevier Taiwan LLC. All rights reserved. doi:10.1016/j.aat.2011.08.002
82
and complications) mechanisms.17 In June 2011, De Oliveria et al18 using the QoR-40 evaluated the dose-dependent effects of dexamethasone on patient recovery after ambulatory gynecological surgery. They found that patients given 0.1 mg/kg of dexamethasone had consumed less opioid painkiller, reported less sore throat, muscle pain, confusion, difficulty in falling asleep, and nausea compared with patients given dexamethasone 0.05 mg/kg of dexamethasone or saline. In summary, we believe that dexamethasone is not only an effective antiemetic but also has beneficial effects on several diverse but interrelated symptoms that determine patient comfort resulting in the overall improved QoR-40 scores. However, only patients with a low-risk unacceptable adverse effects were enrolled in most of the clinical trials. The impact of dexamethasone on outcomes in high-risk patients is not known. The review of Ho et al11 on the studies in the space from 2004 to 2011 on evaluating the potential adverse effects after administering antiemetic doses of dexamethasone reveals that the influence of dexamethasone on glycemia is only short lasting. Even in obese patients with impaired glucose tolerance, the hyperglycemic response is more pronounced but not substantially different when dexamethasone is added in antiemetic treatment. Thus, the benefits of administering dexamethasone should be weighed against the potential side effects of hyperglycemia. However, the limited data were likely unable to detect the uncommon adverse events particularly related to steroids (e.g. impaired wound-healing, postoperative infection) in high-risk patients. Additional large-scale investigations should be made to define the benefits and risks of dexamethasone in the surgical setting, as well as to establish the optimal dose of dexamethasone required to improve postoperative recovery. References 1. Knapp MR, Beecher HK. Postanesthetic nausea, vomiting and retching. J Am Med Assoc 1956;160:376–85. 2. Watcha MF, White PF. Postoperative nausea and vomiting: its etiology, treatment, and prevention. Anesthesiology 1992;77:162–84. 3. Kovac AL. Prevention and treatment of postoperative nausea and vomiting. Drugs 2000;59:213–43. 4. White PF, Watcha MF. Are new drugs cost-effective for patients undergoing ambulatory surgery? Anesthesiology 1993;78:2–5. 5. Aapro MS, Alberts DS. Dexamethasone as an antiemetic in patients treated with cisplatin. N Engl J Med 1981;305:520. 6. Baxendale BR, Vater M, Lavery KM. Dexamethasone reduces pain and swelling following extraction of third molar teeth. Anaesthesia 1993;48:961–4.
Editorial View 7. Wang JJ, Ho ST, Tzeng JI, Tang CS. The effect of timing of dexamethasone administration on its efficacy as a prophylactic antiemetic for postoperative nausea and vomiting. Anesth Analg 2000;91:136–9. 8. Henzi I, Walder B, Tramèr MR. Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review. Anesth Analg 2000;90:186–94. 9. Haynes R. Adrenocorticotropic hormone: adrenocortical steroids and their synthetic analogs-inhibitors of the synthesis and actions of adrenocortical hormones. In: Gilman AG, Gilman LS, Rall TW, Murad F, editors. The pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press; 1990. p. 1447–8. 10. Eberhart LH, Morin AM, Georgieff M. Dexamethasone for prophylaxis of postoperative nausea and vomiting. A meta-analysis of randomized controlled studies. Anaesthesist 2000;49:713–20 [in German]. 11. Ho CM, Wu HL, Ho ST, Wang JJ. Dexamethasone prevents postoperative nausea and vomiting: benefit versus risk. Acta Anaesthesiol Taiwan 2011;49:100–4. 12. Myles PS, Weitkamp B, Jones K, Melick J, Hensen S. Validity and reliability of a postoperative quality of recovery score: the QoR-40. Br J Anaesth 2000;84: 11–5. 13. Herrera FJ, Wong J, Chung F. A systematic review of postoperative recovery outcomes measurements after ambulatory surgery. Anesth Analg 2007;105:63–9. 14. Murphy GS, Szokol JW, Greenberg SB, Avram MJ, Vender JS, Nisman M, et al. Preoperative dexamethasone enhances quality of recovery after laparoscopic cholecystectomy: effect on in-hospital and postdischarge recovery outcomes. Anesthesiology 2011;114:882–90. 15. Yared JP, Starr NJ, Hoffmann-Hogg L, Bashour CA, Insler SR, O’Connor M, et al. Dexamethasone decreases the incidence of shivering after cardiac surgery: a randomized, double-blind, placebo-controlled study. Anesth Analg 1998;87: 795–9. 16. Bisgaard T, Klarskov B, Kehlet H, Rosenberg J. Preoperative dexamethasone improves surgical outcome after laparoscopic cholecystectomy: a randomized double-blind placebo-controlled trial. Ann Surg 2003;238:651–60. 17. Murphy GS, Sherwani SS, Szokol JW, Avram MJ, Greenberg SB, Patel KM, et al. Small-dose dexamethasone improves quality of recovery scores after elective cardiac surgery: a randomized, double-blind, placebo-controlled study. J Cardiothorac Vasc Anesth 2011 [Epub ahead of print]. 18. De Oliveira Jr GS, Ahmad S, Fitzgerald PC, Marcus RJ, Altman CS, Panjwani AS, et al. Dose ranging study on the effect of preoperative dexamethasone on postoperative quality of recovery and opioid consumption after ambulatory gynaecological surgery. Br J Anaesth 2011 [Epub ahead of print].
Yi Lee, Associate Professor Department of Anesthesiology, Buddhist Tzu-Chi General Hospital, Buddhist Tzu-Chi University School of Medicine, Hualien, Taiwan, R.O.C. E-mail: [email protected] Jann-Inn Tzeng, Professor and Chairman* Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan, R.O.C. E-mail: [email protected] (J.-I. Tzeng). * Corresponding author.