BJA Advance Access published June 13, 2011
British Journal of Anaesthesia Page 1 of 10doi:10.1093/bja/aer156 Dose ranging study on the effect of preoperativedexamethasone on postoperative quality of recoveryand opioid consumption after ambulatory gynaecologicalsurgeryG. S. De Oliveira Jr, S. Ahmad, P. C. Fitzgerald, R.J. Marcus, C. S. Altman, A. S. Panjwani and R. J. McCarthy*Department of Anesthesiology, Northwestern University Feinberg School of Medicine, 251 E. Huron St., Feinberg 5-704, Chicago,IL 60611, USA* Corresponding author. E-mail: Background. Glucocorticoids are commonly administered before ambulatory surgery,although their effects on quality of recovery are not well characterized. The purpose of this study was to evaluate the dose-dependent effects of dexamethasone on patient recovery using the Quality of Recovery 40 questionnaire (QoR-40) after ambulatory surgery.
Methods. This prospective, double-blind trial studied 106 female subjects undergoing outpatient gynaecological laparoscopy. Subjects were randomized to receive saline, dexamethasone 0.05 mg kg21 or dexamethasone 0.1 mg kg21 before induction. The primary outcome was global QoR-40 at 24 h. Postoperative pain, analgesic consumption, side-effects, and discharge time were also evaluated.
Results. Global median (IQR) QoR-40 after dexamethasone 0.1 mg kg21 193 (192–195) was greater than dexamethasone 0.05 mg kg21 179 (175–185) (P¼0.004) or saline, 171 (160– 182) (P,0.005). Median (IQR) morphine equivalents administered before discharge were 2.7 (0–6.3) mg after dexamethasone 0.1 mg kg21 compared with 5.3 (2.4–8.8) mg and 5.3 (2.7–7.8) mg after dexamethasone 0.05 mg kg21 and saline (P¼0.02). Time to meet discharge criteria was 30 min shorter after dexamethasone 0.1 mg kg21 compared with saline (P¼0.005). At 24 h, subjects receiving dexamethasone 0.1 mg kg21 had consumed less opioid analgesics, reported less sore throat, muscle pain, confusion, difficulty in falling asleep, and nausea compared with dexamethasone 0.05 mg kg21 and saline.
(0.05 mg kg-1), a reduction inopioid consumption, and Conclusions. Dexamethasone demonstrated dose-dependent effects on quality of recovery.
Dexamethasone 0.1 mg kg21 reduced opioid consumption compared with dexamethasone 0.05 mg kg21, which may be beneficial for improving recovery after ambulatory Keywords: anaesthesia; general, gynaecological, recovery; recovery, postoperative, pain, postoperative, dexamethasone, postoperative nausea and vomiting Single dose glucocorticoids such as dexamethasone are Corticosteroids may have other beneficial or detrimental commonly administered perioperatively to ambulatory effects on patient recovery. They can generate a subjective surgery patients. Preoperative dexamethasone has an estab- sense of well-being, independently of their disease status, lished role in nausea and vomiting prThe effect of which can lead to a faster discharge from the In steroids in reducing postoperative pain and opioid consump- addition, the anti-inflammatory effects of dexamethasone tion have been demonstrated after ambulatory surgery; may decrease the incidence and severity of airway morbidity although these effects have primarily been demonstrated which may lead to patient dissatisfaction after anaesthesia at high doses of steroids that are not routinely used in clinical and surConversely, corticosteroids can produce practice.High doses of steroids are also associated with symptoms of insomnia and depression that may delay the side-effects such as hyperglycaemia and immune suppres- return to daily activities, a primary goal in outpatient sion which may delay discharge or result in a hospital surThe dose dependency of these effects has not been well characterized after ambulatory surgery.
& The Author [2011]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.
For Permissions, please email: [email protected] The Quality of Recovery 40 questionnaire (QoR-40) is a maintain the TOF between 1 and 3 twitches. During mainten- multidimensional instrument that was specifically developed ance, patients received a mixture of air and oxygen to keep and validated to evaluate the health status of patients after FIO between 0.4 and 0.6. All gases were delivered though anaesthesia and surgery.It can be particularly useful when a humidified circuit. All patients had an orogastric tube an intervention affects various aspects of patient recovery, as is the case for corticosteroids such as dexamethasone. The At the end of the procedure, at removal of the laparo- purpose of this study was to evaluate the dose-dependent scopic instruments, the remifentanil infusion was stopped effects of dexamethasone on the quality of recovery, post- and the patient received hydromorphone 10 mg kg21 i.v.
operative airway morbidity, and opioid analgesic use after Neuromuscular blockade was antagonized using neostig- mine 0.05 mg kg21 and glycopyrrolate 0.01 mg kg21. Patientsalso received ketorolac 30 mg i.v., ondansetron 4 mg, andmetoclopramide 10 mg before the end of the procedure.
Before extubation, the subject’s mouth was suctioned with This study was a prospective, randomized, double-blind a 14 French soft suction catheter and the presence of placebo controlled trial. Clinical trial registration for this blood in the aspirate was noted. Subjects were extubated when they were able to perform a 5-s head lift and follow identified: NCT01052038. Study approval was obtained from the Northwestern University Institutional Review Board, and In the post-anaesthesia recovery room, subjects were written informed consent was obtained from all the study asked to rate their pain upon arrival and at regular intervals participants. Eligible subjects were ASA physical status I on a 0–10 numeric rating scale (NRS) for pain, where 0 and II females undergoing outpatient gynaecological laparo- means no pain and 10 is the worst pain imaginable.
scopy. Patients with a history of recent respiratory tract infec- Nausea and vomiting were also assessed at the same inter- tion (,1 month), current use of an opioid analgesic or vals and recorded as present or absent. Hydromorphone corticosteroid, pregnancy, or anticipated difficult airway 0.2 mg i.v. was administered every 5 min to maintain an were not enrolled. Reasons for exclusion from the NRS pain score ,4 of 10. The time to first hydromorphone study after study drug administration included: difficult administration was recorded. Discharge readiness was airway defined by more than two laryngoscopic attempts assessed by using the Post Anesthesia Discharge Scoring by the attending anaesthesiologist and conversion from a System (Pscored every 15 min until patients met dis- laparoscopic to an open laparotomy. A bedside airway exam- charge criteria. At discharge, subjects were instructed to take ination was performed and the Mallampati classification was ibuprofen 400 mg orally for mild pain (,4 of 10) or hydroco- recorded. Subjects were randomized using a computer- done 10 mg plus paracetamol 325 mg for pain . 4 of 10 generated table into three groups: saline, dexamethasone 0.05 mg kg21, and dexamethasone 0.1 mg kg21. Group Subjects were assessed at 1, 3, and 24 h after the pro- assignments were sealed in sequentially numbered opaque cedure and were asked about the presence or absence of a envelopes that were opened by a research nurse not involved sore throat and to rate pain related to the sore throat at with the subjects’ care. The study drug was administered in rest and with swallowing using an NRS for pain (where 0 is 100 ml of normal saline as an infusion over 10 min, when no pain and 100 is the worst sore throat pain ever experi- the patient was in the preoperative holding area. The anaes- enced by the patient). At 3 h after the surgery, they were thesia care team was blinded to group allocation.
also questioned regarding the presence of cough using a pre- All subjects were premedicated with 0.04 mg kg21 intrave- viously describedgrading scale where 0¼no cough or nous (i.v.) midazolam. Propofol 1–2 mg kg21 was adminis- scratchy throat, 1¼minimal scratchy throat or cough, 2¼ tered for anaesthesia induction, a remifentanil infusion (0.1 moderate cough similar to a cold, or 3¼severe cough, mcg kg21 min21) was begun, and rocuronium 0.6 mg kg21 greater than a cold. The presence and severity of hoarseness i.v. was administered to induce muscle paralysis. Subjects was also evaluated as 0¼no evidence of hoarseness occur- were ventilated via a face mask until disappearance of all ring any time since your operation, 1¼no evidence of hoarse- twitches on the train-of-four (TOF) monitor (EZ Stim II, Life ness at the time of interview, but hoarseness was present Tech, Stafford, TX, USA). Tracheal intubation was initially previously, 2¼hoarseness at the time of interview, that was attempted by an anaesthesia resident physician or a certified noted only by the patient, or 3¼hoarseness that was easily registered nurse anaesthetist under supervision of an attend- ing anaesthesiologist. The number of intubation attempts, Subjects were contacted 24 h after the procedure by an total time to intubation, and the need for cricoid pressure investigator unaware of group allocation and were asked to improve laryngoscopy grade were recorded. Anaesthesia about analgesic consumption and the QoR-40 questionnaire maintenance was achieved using remifentanil, titrated to was administered (Table ). Perioperative data collected keep the mean arterial pressure within 20% of baseline, included subject’s age, height, weight, American Society of and sevoflurane titrated to bispectral index (Aspect Medical Anaesthesiologist physical class, surgical duration, intra- System Inc., Norwood, MA, USA) between 40 and 60.
operative remifentanil use, total i.v. fluids, and total Additional doses of rocuronium were administered to Effects of dexamethasone on quality of recovery after surgery The primary outcome measure was the global QoR-40 The Shapiro–Wilks, Anderson–Darling and Kolmogorov– aggregate score. Global QoR-40 scores range from 40 to 200 Smirnov tests were used to test the hypothesis of normal distri- for representing very poor to outstanding quality of recovery.
bution. Normally distributed interval data are reported as mean The mean QoR-40 in female patients after anaesthesia and [standard deviation (SD)] and were evaluated with one-way surgery has been reported to be 162, and the sample was esti- ANOVA. Non-normally distributed interval data and ordinal mated to detect a difference of 10 points in the quality of data are reported as median [interquartile range (IQR) or recovery among the dexamethasone and placebo groups.A median absolute deviation (MAD)] and were analysed using sample size of 34 per group was estimated for the three the Kruskal–Wallis H test. Post hoc comparisons were made study groups to be compared. The total sample of 102 sub- using the Tukey–Kramer or Dunn’s test with Bonnferoni correc- jects achieves 81% power to detect differences among the tion for multiple comparisons. Categorical variable were evalu- means using an F-test and a one-way analysis of variance ated using a x2 statistic. Estimates of exact P-values were at a 0.05 significance level. The common standard deviation determined for the x2 and the Mann–Whitney test using a within a group was assumed to be 26.To account for drop- Monte Carlo method with 10 000 samples and confidence outs, 120 subjects were randomized. The sample size calcu- limits of 99%. All reported P-values are two-tailed. Statistical lation was made using PASS version 8.0.13 release date 14 analysis was performed using NCSS 2007 7.1.20, release date January 2010 (NCSS, LLC, Kaysville, UT, USA).
19 February 2010 (NCSS, LLC, Kaysville, UT, USA) and IBMwSPSSw Statistics 19 (Version 19.0.0, IBM Corporation, Somers NY).
Table 1 Quality of recovery questionnaire 40 (QoR-40). All items scored on a five-point (1–5) Likert scale. Positive characteristics scored 1¼noneof the time to 5¼all of the time. Negative characteristics scored 5¼none of the time to 1¼all of the time Feeling angryFeeling depressedFeeling aloneHad difficulty falling asleep Have normal speechAble to wash, brush teeth, shaveAble to look after your own appearanceAble to writeAble to return to work/usual home activities Able to communicate with family/friendsAble to communicate with visiting healthcare workerHaving support from family/friendsGetting support from visiting healthcare workerAble to understand instructions and advice Moderate painSevere painHeadacheMuscle painsBackacheSore throatSore mouth Excluded (n = 26):Did not meet inclusion criteria (n = 17)Patient refused (n = 9) Received intervention (n = 40) Received intervention (n = 40) Received intervention (n = 40) Protocol violations (n = 3) Difficult intubation (n = 1) Difficult intubation (n = 1) Excluded from analysis (n = 4) Excluded from analysis (n = 6) Excluded from analysis (n = 4) Responses to individual items of the QoR-40 in the phys- ical comfort, emotional state, psychological support, and The details of the conduct of the study are shown in Figure pain dimension that demonstrated differences among One hundred and twenty subjects were randomized and 106 groups are shown in Table The effect of dexamethasone completed the study. Patients were enrolled consecutively 0.05 mg kg21 on recovery scores are most apparent in phys- from January 2010 through September 2010. Patient’s base- ical comfort dimension in restfulness and reduced retching line characteristics and surgical factors were not different compared with saline. In the other QoR-40 dimensions, anxiousness, bad dreams, and moderate pain were reduced The median (IQR) global recovery score (QoR-40) 24 h compared with saline. The effects of dexamethasone 0.1 after discharge in the dexamethasone 0.1 mg kg21 group mg kg21 compared with saline were seen in all dimensions was 193 (192–195) which was greater than the score for of the QoR-40 questionnaire. In addition, dexamethasone the dexamethasone 0.05 mg kg21, 179 (175–185) 0.1 mg kg21 demonstrated a greater effect on sore throat (P¼0.004) or saline, 171 (160–182) groups (P,0.005). The and muscle pain, reduced confusion, difficulty in falling dimensions of the QoR-40 questionnaire are shown in asleep and a reduced median nausea score compared with Figure The dexamethasone 0.01 mg kg21 group reported higher median scores in every dimension of the QoR-40 com- NRS pain scores and opioid consumption in the first hour pared with saline and in the physical independence and pain in the recovery room did not differ among groups (Table ).
dimensions compared with dexamethasone 0.05 mg kg21.
Cumulative opioid consumption by discharge was lower in Effects of dexamethasone on quality of recovery after surgery Table 2 Subject characteristics preoperative and operative data. Data presented as mean(SD), median (IQR), or n(%) Saline (n536) Dexamethasone 0.05 mg kg21 (n534) Dexamethasone 0.1 mg kg21 (n536) P-value with saline at 3 and 24 h (Table The presence of sore throat was less in the dexamethasone 0.1 mg kg21 group compared with saline at 24 h, but the incidence and severity Dexamethasone 0.05 mg kg–1 (n=34)Dexamethasone 0.1 mg kg–1 (n=36) was not different between dexamethasone groups. The severity of coughing among the groups was similar at 3 h, but less at 24 in the dexamethasone 0.1 mg kg21 group com- pared with dexamethasone 0.05 mg kg21 or saline. Hoarse- ness was reduced in patient perceived severity in the dexamethasone 0.1 mg kg21 group compared with dexa- methasone 0.05 mg kg21 and saline groups at 3 and 24 h. Time to meet discharge criteria was decreased after dexa-methasone 0.1 mg kg21 compared with the saline. Post dis- charge 24 h opioid/paracetamol consumption was less in the 0.1 mg kg21 dexamethasone group compared with dexa- methasone 0.05 mg kg21 and saline. Ibuprofen consumption did not differ among groups in the first 24 h.
Fig 2 Box plot of dimensions of QoR-40 questionnaires completed 24 h after outpatient gynecological laparoscopic surgery. Median The important finding of this study was the dose-dependent values shown as solid line within box of 25 and 75th percentile effect of dexamethasone on quality of recovery after outpa- values. Whiskers represent 5th and 95th percentile values. Single tient gynaecological surgery. Dexamethasone 0.1 mg kg21 daggers mean different from saline, P¼0.05. Double daggersmean different from dexamethasone 0.05 mg kg21, P¼0.05.
but not 0.05 mg kg21 reduced nausea and vomiting and Data were compared using the Kruskal–Wallis and the multiple opioid consumption in the recovery room, sore throat, cough- comparison Z-value test (Dunn’s test) with Bonferroni correction.
ing, and hoarseness at 3 h post-surgery and reduced time todischarge readiness. The quality of the post-discharge recov-ery assessed at 24 h was improved with dexamethasone 0.1 the 0.1 mg kg21 dexamethasone group compared with the mg kg21 compared with both saline and dexamethasone dexamethasone 0.05 mg kg21 group and saline groups.
0.05 mg kg21. Patients receiving dexamethasone 0.1 mg The presence and intensity of sore throat at 1 h was similar kg21 reported improvement in physical, emotional, psycho- among groups but both the incidence and severity of sore logical, and pain domains compared with placebo. They throat were less in the dexamethasone groups compared also had less severe airway morbidities at 24 h. Most Table 3 Differences in QoR-40 items among groups. Data presented as median (MAD). †Different from saline. ‡Different from dexamethasone,0.05 mg kg21. Data analysed using the Kruskal–Wallis H test. Post hoc comparisons made using Dunn’s test with Bonnferoni correction at acorrected P¼0.05. *¼All items scored on a five-point (1–5) Likert scale. }Positive characteristics score range; 1¼none of the time to 5¼all of thetime. §Negative characteristics score range; 1¼all of the time to 5¼none of the time Effects of dexamethasone on quality of recovery after surgery importantly, opioid consumption in the first 24 h after dis- lower pain scores in the immediate postoperative period on charge was reduced with dexamethasone 0.1 mg kg21.
subjects receiving 5 mg dexamethasone for outpatient ano- A major determinant for discharge after ambulatory rectal surgery compared with however, in patients surgery is the quality of postoperative pain contrIn undergoing sinus surgery, Al-Qudah and colleagues did not addition to the direct influence of pain on readiness to dis- find a difference in postoperative pain scores when compar- charge, side-effects of opioid analgesics such as nausea, ing 8 mg of dexamethasone with placebo.Jokela and col- vomiting, sedation, and urinary retention can also delay dis- leagues demonstrated that 10 and 15 mg of dexamethasone charge time. The dose-related effects of dexamethasone had opioid sparing effects after laparoscopic hysterectomy.
observed in this study have important clinical implications Likewise, Haval and colleagues demonstrated lower VAS since practice guidelines for prevention of postoperative scores at 24 h compared with placebo when 16 mg of dexa- nausea and vomiting after ambulatory surgery favour theuse of the 0.05 mg kg21 dose.Another factor that may methasone was administered to patients undergoing outpa- delay discharge and prolong recovery room stay after ambu- tient breast surgery.The results of the aforementioned latory surgery is the presence of a sore throat since pain studies together with the results of the current study related to the sore throat could make patients reluctant to suggest that the analgesic and opioid-sparing effect of dexa- go home.Dexamethasone 0.05 and 0.1 mg kg21 reduced methasone varies with the dose of dexamethasone adminis- sore throat pain compared with saline at 3 h which may tered as well as the type of surgical procedure. We restricted have contributed to a faster discharge process. The reduced our study to a single type of surgery, outpatient gynaecologi- airway morbidity at 24 h in the dexamethasone 0.1 mg cal laproscopy, and demonstrated that dexamethasone 0.1 kg21 group compared with both dexamethasone 0.05 mg mg kg21 provided effective multimodal analgesia; however, kg21 and saline represents additional evidence of improved we cannot generalize our finding to other surgical Multimodal analgesic techniques are frequently used to Several studies in ambulatory patients have evaluated improve postoperative pain management and reduce quality of recovery primarily as improvement in postoperative opioid-related Several strategies including pain, nausea, and vomiting;–however, this approach has i.v. local anaesthetics, non-steroidal anti-inflammatory limited significance when not adjusted for patient’s level of activity, emotional status, and independence. In the current study, we used the QoR-40 questionnairdesigned antagonists have been demonstrated to be effective after to measure patient’s health status after surgery and outpatient surgery.The effect of corticosteroids on post- anesth–In a review of postoperative recovery operative analgesia has not been as consistently demon- assessment measures after ambulatory surgery, the strated, and this may represent the wide variation in QoR-40 was the only test that fulfilled the criteria of: appro- dexamethasone dosage studied. Wu and colleagues reported priateness, reliability, validity, responsiveness, precision, Table 4 Postoperative pain management, side-effects, and time to discharge. Data presented as median (IRQ) or n(%). †Different from saline.
‡Different from dexamethasone 0.05 mg kg21. Post hoc comparisons made using Dunn’s test with Bonnferoni correction to P¼0.05. §Twosubjects in saline group and two subjects in dexamethasone 0.05 mg kg21 group admitted for 23 h observation excluded from analysis NRS for painPost anaesthesia care unit admission Required opioid in post anaesthesia recovery room [n(%)] Time to first opioid administration (min) Cumulative opioid consumption (iv morphine equivalents)First hour after operation Hoarseness (none/previous/noted only by patient/easily noticed) Pain medication consumption in the first 24 h after discharge interpretability, acceptability, and feasibilityThe authors correlated. Therefore, we believe that the differences found did note that the QoR-40 was not specifically designed for in QoR-40 in this study represent clinically significant use in ambulatory surgery and therefore the clinical correlate improvement in recovery with dexamethasone compared of the change in global QoR-40 values such as those observed in this study are difficult to assess. The responsive- Improved self-reported quality of recovery and reduced ness of this instrument has been assessed in patients evalu- emetic symptoms at 24 h after discharge for dexamethasone ated before and after surThe calculated standardized 4 mg vs control after ambulatory laparoscopic cholecystect- response mean of 0.65 was suggested by the authors to rep- omy has previously been reported.The QoR scale used in resent sensitivity of the instrument to clinically significant the aforementioned study was based on a 0–100 self- changes. In a study of outcomes after cardiac surgery, a reported scale and did not evaluate the domains of recovery.
poorer quality of life at 3 months was found in subjects We found that dexamethasone 0.05 mg kg21 primarily that had median QoR-40 global values 10 points less than affected the physical comfort sphere of recovery; whereas those with higher QoR-40 values 3 days after cardiac dexamethasone 0.1 mg kg21 improved recovery in all surDays 1 and 3 QoR-40 values were highly domains of the QoR-40. It is likely that at the 0.05 mg kg21 Effects of dexamethasone on quality of recovery after surgery dose the effects of dexamethasone on the QoR-40 most estimates were similar for all cases, the dexamethasone likely reflect its antiemetic actions, but at 0.1 mg kg21 0.05 mg kg21 group did have more pain ablation procedures, analgesic and euphoric effects are likely to have contributed were slightly longer and required more intraoperative remi- to the increase in QoR-40 scores. Patients might have the fentanil on examination compared with the saline and dexa- same level of analgesia assessed by visual analogue scale methasone 0.1 mg kg21 group, which may have affected the scores but cannot be compared in terms of quality of recov- findings of the study. There were, however, no differences in ery if they are unable to resume normal daily activities. In the time to meet discharge criteria (P¼0.9), opioid consumption current study, dexamethasone 0.1 mg kg21 produced better before discharge (P¼0.3), or global QoR-40 scores (P¼0.5) physical comfort score (nausea, vomiting, retching, sleep, among the surgical procedure groups. The effects of the ability to eat). They also had greater physical independence dexamethasone on quality of recovery observed in this scores. The higher dexamethasone group not only had less study were in addition to the effects of ketorolac, metaclo- pain but they were also more active 24 h after surgery.
pramide, and ondansetron which were administered to all These finding have important economic implication when evaluating costs associated with ambulatory procedures.
In conclusion, we demonstrated that 0.1 mg kg21 of dexa- The mechanism of the analgesic effect of dexamethasone methasone produced a better quality of recovery with less is multifactorial. It has anti-inflammatory properties by inhi- postoperative pain and better return to normal daily activi- bition of phospolipase-A2, cytokines production, and decreas- ties after outpatient gynaecological laproscopic surgery ing polymorphonuclear leucocyte function, suppresses the when compared with 0.05 mg kg21 of dexamethasone and production of free oxygen radicals and nitric oxide by endo- placebo. The higher dexamethasone dose also produced an thelial cells,and reduces postoperative oedema.We opioid-sparing effect, which may be beneficial for improving suspect that the anti-inflammatory effects of dexametha- sone may be responsible for the reduced clinical symptoms of airway morbidity, since the acute inflammatory reaction produced by the presence of the tracheal tube or direct trauma to the airway mucosa are believed to be mechanisms for the development of postoperative sore throat after pro-cedures requiring tracheal intubation.– We administered dexamethasone before the patient was Support was provided solely by institutional and/or depart- taken to the operating room rather than after induction of anaesthesia which is more commonly done in clinical prac-tice. We did this to optimize the effect of dexamethasone (peak effect 45 min to 1 h) on the stress response during sur- 1 Karanicolas PJ, Smith SE, Kanbur B, Davies E, Guyatt GH. The gical incision and other stress generating portions of surgery impact of prophylactic dexamethasone on nausea and vomiting especially during the short ambulatory procedures studied.
after laparoscopic cholecystectomy: a systematic review and Also, because dexamethasone can produce an excruciating meta-analysis. Ann Surg 2008; 248: 751–62 perineal burning in 50–70% of patients, we administered 2 Aasboe V, Raeder JC, Groegaard B. Betamethasone reduces post- the drug slowly over 10 min diluted in 50 ml of saline.
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Ogunnaike B. Effect of short-term postoperative celecoxib

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