The Effect of Preoperative Dexamethasone on the Immediate and by alicejenny


									The Effect of Preoperative Dexamethasone on the Immediate
and Delayed Postoperative Morbidity in Children Undergoing
Ana Lucia S. Pappas, MD*, Radha Sukhani, MD*, Andrew J. Hotaling, Mm,
Marianna Mikat-Stevens,  MD*, Joseph J. Javorski, MD*, Joseph Donzelli, MDt, and
Kalavathi Shenoy, MD*
Departments      of *Anesthesiology           and tOtolaryngology,          Head and Neck Surgery,       Loyola   University         Medical     Center,
Maywood,    Illinois

         In this      prospective,         randomized,       double-blind,         incidence of PONV, need for rescue antiemetics, quality
         placebo-controlled         study, we examined the effect of               of oral intake, and analgesic requirements            did not differ
         preoperative      dexamethasone        on postoperative       nausea      between groups. However, during the 24 h after dis-
         and vomiting (PONV) and 24-h recovery in children                         charge, more patients in the control group experienced
         undergoing       tonsillectomy.      One hundred        thirty chil-      PONV (62% vs 24% in the steroid group) and com-
         dren, 2-12 yr of age, ASA physical status I or II, com-                   plained of poor oral intake. Additionally,           more children
         pleted the study. All children received oral midazolam                    in the control group (8% vs 0% in the steroid group)
         0.5-0.6 mg/kg          preoperatively.      Anesthesia       was in-      returned to the hospital for the management                of PONV
         duced with halothane and nitrous oxide in 60% oxygen                       and/or poor oral intake. The preoperative              administra-
         and maintained        with nitrous oxide and isoflurane. In-               tion of dexamethasone       significantly     decreased the inci-
         tubation was facilitated by mivacurium                 0.2 mg/kg.          dence of PONV over the 24 h after home discharge in
         Each child received fentanyl 1 pg/kg IV before initia-                     these children.     Implications:       In this double blind,
         tion of surgery, as well as dexamethasone                  1 mg/kg        placebo-controlled     study, we examined the efficacy of a
         (maximal dose 25 mg) (steroid group) or an equal vol-                      single large dose (1 mg/kg; maximal dose 25 mg) of
         ume of saline (control group). Intraoperative                  fluids     preoperative       dexamethasone          on posttonsillectomy
         were standardized          to 25-30 mL/kg lactated Ringer’s               postoperative nausea and vomiting (PONV) in children
         solution. All tonsillectomies        were performed under the              2-12 yr of age undergoing           tonsillectomy.      Compared
         supervision of one attending surgeon using an electro-                     with placebo, dexamethasone            significantly     decreased
         dissection     technique.      Postoperatively,     fentanyl and           the incidence of PONV in the 24 h after discharge, im-
         acetaminophen        with codeine elixir were administered                 proved oral intake, decreased the frequency of parental
         as needed for pain. Rescue antiemetics were adminis-                       phone calls, and resulted in no hospital returns for the
         tered when a child experienced two episodes of retch-                      management of PONV and/or poor oral intake.
         ing and/or        vomiting.      Before home discharge,            the                                    (Anesth Analg 1998;87:57-61)

T                   and adenoidectomy are the major
         onsillectomy                                                              pain, poor oral intake, dehydration and fever, how-
      ambulatory surgical procedures most frequently                               ever, continues to be a concern in children undergoing
      performed in children (1). The safety of these                               tonsillectomy in an ambulatory setting (6,7). The re-
procedures in the ambulatory setting has been well                                 ported incidence of PONV after tonsillectomy is 40%-
documented (l-4). The introduction of an electrodis-                               73% (8-10). Several anesthetic and antiemetic regi-
section surgical technique has virtually eliminated im-                            mens have been used to minimize PONV with
mediate postoperative hemorrhage (5). Morbidity re-                                variable success (8-12).
lated to postoperative nausea and vomiting (PONV),                                    In children undergoing tonsillectomy, dexametha-
                                                                                   sone and other steroid preparations have been used to
                                                                                   minimize tissue injury and edema and related mor-
                                                                                   bidity, such as pain, fever and poor oral intake (13-16).
  Accepted      for publication March   31, 1998.                                  The prolonged antiemetic effect of IV dexamethasone
  Address      correspondence     and reprint      requests      to Ana Lucia
Pappas,    MD,     Department   of Anesthesiology,         Loyola     University   is well documented in chemotherapy-induced nausea
Medical    Center, 2160 South First Avenue,        Maywood,        IL 60153.       and vomiting (17). The effect of dexamethasone in

01998 by the International   Anesthesia   Research   Society
0003-2999/98/$5.00                                                                                                          Anestb     Analg   1998;87:57-61   57
58    PEDIATRIC    ANESTHESIA           PAPPAS   ET AL.                                                                            ANESTH       ANALG
      DEXAMETHASONE,          CHILDREN,       AND ADENOTONSILLECTOMY                                                                    1998;87:57-61

tonsillectomy-associated        PONV, however,       is contro-               All tonsillectomies         were performed           using an elect-
versial (15,16,18). Because PONV is a multifactorial                      rodissection      technique under the supervision                   of one
problem, these conflicting results could be related to                    attending surgeon (AJH) who was also responsible for
the lack of standardization         of anesthetic and periop-             grading the degree of tonsillar enlargement (1 = ton-
erative factors that contribute         to the incidence and              sils within      tonsillar      folds, 2 = tonsils just outside
severity of PONV.                                                         tonsillar folds, 3 = tonsils well outside tonsillar folds
   The purpose of the present study was to determine                      but not reaching uvula, 4 = tonsils reaching uvula or
whether one single, large dose of IV dexamethasone                        past uvula). At the conclusion of surgery, gastric con-
administered      before surgery       could decrease PONV                tents were suctioned via an orogastric tube. Drugs to
and improve oral intake in the first 24 h after home                      reverse muscle relaxation were not required in any
discharge. To specifically delineate the contribution         of          case. The children were tracheally                    extubated when
dexamethasone,        all anesthetic and nonanesthetic      fac-          they awoke and demonstrated                   satisfactory       motor re-
tors that could influence the incidence of PONV were                      covery. Children were transported                  to the postanesthe-
standardized.                                                             sia care unit (PACU 1); when they were fully awake,
                                                                          comfortable,       and stable, they were transferred                   to a
                                                                          step-down       recovery unit (PACU 2). All children were
                                                                          observed in the PACU for a combined period of at
Methods                                                                   least 180 min. Oral fluids were offered to the children
After institutional      review board approval,             130 chil-     but they were not required to take them. Children had
dren, 2-12 yr of age, ASA physical status I or II, who                    to be able to swallow              without    difficulty     before they
were scheduled for ambulatory             tonsillectomy      and ad-      were discharged            home. Children            were considered
enotonsillectomy       were enrolled in the study. Written,               ready for discharge when they met institutional                       crite-
informed parental consent was obtained in all cases.                      ria: they were awake, alert, comfortable,                    and able to
The study design was randomized,                double-blind,      and    swallow     without      difficulty and had stable vital signs,
placebo-controlled.       Children who received antiemet-                 minimal or no nausea, and no retching and vomiting.
its, antihistaminics,       steroids, or psychoactive           drugs     Parents participated           in the child’s care for the entire
within 24 h of surgery were excluded, as were chil-                       PACU stay.
dren who had a history of diabetes and those in whom                          All vomiting        or retching episodes during PACU
IV induction was indicated; e.g., those with gastro-                      stay were recorded by the PACU nurse caring for the
esophageal reflux. Children were allowed to eat solid                     child. For the purposes of data collection, only retch-
food until 12 AM on the day before surgery and to have                    ing and vomiting episodes were documented, because
clear liquids until 3 h before the expected start of                      nausea is difficult to assess in children. Episodes of
surgery.                                                                  retching and vomiting occurring                  <5 min apart were
    All children       received      oral midazolam           0.5-0.6     considered one episode. A rescue antiemetic (metoclo-
mg/kg      (maximal dose 20 mg) for preanesthetic                med-     pramide 0.15 mg/kg)                was administered           IV when a
ication 2030 min before anticipated induction. After                      child experienced           two episodes of retching and/or
establishing     standard monitoring,          general anesthesia         vomiting.      If metoclopramide             did not control retch-
was induced using halothane and a gas mixture of                          ing and/or        vomiting        after 20 min, a second rescue
60% nitrous oxide and oxygen. IV access was estab-                        antiemetic        (ondansetron            0.15 mg/kg             IV) was
lished after the induction of anesthesia. The amount of                   administered.
IV fluid administered            was standardized          to 25-30           The need for postoperative                pain medication          was
mL/kg      of lactated Ringer’s solution during the intra-                assessed by the PACU nurses. IV fentanyl in incre-
operative period, followed by a maintenance-rate                    in-   ments of 0.5 pg/kg was given for pain during early
fusion until discharge. Endotracheal               intubation      was    recovery until the child was comfortable.                       Once chil-
facilitated by mivacurium          0.2 “g/kg.      Anesthesia was         dren demonstrated            the ability to swallow,            they were
maintained with nitrous oxide and isoflurane adjusted                     given acetaminophen                  with    codeine        elixir (0.75-
to maintain       heart rate and blood pressure                values     1 mg/kg      codeine) to control pain. Children were of-
within 20% of the baseline induction value. Each child                    fered liquids 45 min after arrival to PACU. The quality
received fentanyl 1 pg/kg before surgery. Dexameth-                       of oral intake was judged as follows: excellent = child
asone 1 mg/kg (maximal dose 25 mg, steroid group)                         requests it, good = child accepts it when offered,
or an equal volume of saline (control group) was                          fair = child accepts it when coaxed, and poor = child
administered       IV in a randomized          double-blind      fash-    refuses.
ion after the induction of anesthesia before surgery.                         All patients were discharged               home with prescrip-
Randomization        was guided by a computer-generated                   tions for acetaminophen               with codeine and plain acet-
number table. The study drugs were prepared by the                        aminophen to be taken concurrently                     every 4 h while
pharmacy,       and an appropriate            code number          was    awake. Parents were instructed                   to follow the pain
assigned.                                                                 medication schedule diligently. An evaluation diary/
ANESTH       ANALG                                                                                     PEDIATRIC        ANESTHESIA      PAPPAS     ET AL.      59
1998;87:5741                                                                 DEXAMETHASONE,            CHILDREN,        AND ADENOTONSILLECTOMY

log book was provided              to parents, and they were                 Table 1. Demographic   Characteristics, Duration of
instructed to record oral intake (graded in the manner                       Anesthesia and Surgery, Oral Intake, and PACU Stay
similar to that in the PACU), number of episodes of                                                                            Steroid             Control
retching      and vomiting,        compliance        with oral pain                                                            group                 group
medications,       and state of hydration              (frequency       of                                                    (n = 63)             (n = 65)
voiding). Parents were asked to call the otolaryngol-                        Age W                                             6.0   t    2.5     5.8   2   2.7
ogy service if the child experienced more than two                           Weight (kg)                                      27.1   ?    13.5   26.0   2   13.3
episodes of vomiting           or had poor oral intake and                   Anesthesia duration (mm)                         62.3   2    18.5   63.0   5   15.3
failed to void for >12 h after surgery. A rescue anti-                       Surgery duration (min)                           39.4   -c   13.3   40.2   k   14.7
emetic (trimethobenzamide                hydrochloride         supposi-      Time to first oral intake in                     84.3   t    28.3   83.6   +   42.3
                                                                                PACU (min)
tory 200 mg for children weighing >15 kg and 100 mg
                                                                             PACU stay duration (min)                        183.1 + 19.1        191.7 + 2&o*
for children weighing         ~15 kg to be administered              ev-
ery 6 h as needed for a maximum of three doses) was                            PACU    = postanesthesia        care unit.
                                                                               * P i 0.05 versus      the steroid   group.
prescribed for the children whose parents had called
and reported more than two episodes of vomiting.
Twenty-four       hours after discharge, one of the investi-
                                                                             with atypical pseudocholinesterase). Of the remaining
gators (ALP or RS) called the parents to document the
                                                                             128 children, 63 received IV dexamethasone (steroid
first 24-h recovery data and compliance with analgesic
                                                                             group) and 65 received saline (control group).
                                                                                There were no significant differences between the
    Age, weight, surgery time, anesthesia time, dura-
                                                                             two groups with respect to age, weight, gender distri-
tion of PACU stay, fentanyl requirement                      in PACU,
                                                                             bution, blood loss during surgery, duration of anes-
incidence of PONV, need for rescue antiemetics, qual-
ity of oral intake in PACU, quality of oral intake after                     thesia and surgery, and time to oral intake (Table 1).
home discharge, compliance with oral pain medica-                            The duration of PACU stay, however, was signifi-
tions, calls to physicians,         and hospital returns were                cantly longer in the control group. Distributions of
documented        for each patient.                                          patients in the two study groups was comparable with
    A postoperative        emesis incidence of 40%-70% has                   respect to tonsillar size, surgical indication, and sur-
been reported         after adenotonsillectomy             in children       gical procedure.
 (B-10). This incidence was taken into consideration                            Incidence of PONV, need for rescue antiemetics,
when selecting the patient sample size for the current                       quality of oral intake, and analgesic requirements
study. A decrease in the incidence rate to 50% was                           were not significantly different between the two
considered to be clinically relevant. It was desired that                    groups before PACU discharge (Table 2). However,
this be detected with a P valve ~0.05 at a power of                          during 24-h period after discharge from the PACU, a
90%. The current study therefore was targeted for a                          significantly greater percentage of patients in the con-
minimal sample size of 110 patients (55 in each group).                      trol group experienced PONV. Parental calls to the
A larger number of children (65 in each group) was                           physician for complaints of pain, inability to maintain
recruited to overcome the factor of parental noncom-                         oral pain medication schedule, poor oral intake, and
pliance and to ensure that the satisfactory                    recovery      PONV were also higher in the control group. Al-
 data could be obtained for the projected number of                          though none of the patients in the steroid group re-
patients determined by power analysis.                                       turned to the hospital, five children in the control
    Student’s t-test was used to analyze group differ-                       group returned to the hospital for the management of
 ences in patient demographics,               duration of surgery,           PONV or for IV hydration in the first 24 h after sur-
 duration of anesthesia, and recovery times. ,$ analysis                     gery. Compared with those in the steroid group, sig-
 and Fisher’s exact test were used as appropriate                       to   nificantly fewer children in the control group had
 compare symptom frequencies.               A P valve CO.05 was              good to excellent oral intake after home discharge
 considered     statistically    significant.     All data are pre-          (Table 2).
 sented as mean -+ SD.                                                          Five children in the steroid group experienced par-
                                                                             tial laryngospasm at induction, and one experienced
                                                                             bronchospasm after intubation. Among the children in
                                                                             the control group, four experienced partial laryngo-
Results                                                                      spasm at induction, and one experienced complete
Of the 130 children enrolled in                 the study, 2 were            laryngospasm at emergence. These complications re-
excluded (1 child had generalized                edema 1 day after           solved with appropriate interventions and did not
surgery and was diagnosed with                 acute glomerulone-            influence patient recovery. All the patients met dis-
phritis unrelated to the procedure;                1 child had pro-          charge criteria and were discharged home from the
longed paralysis after mivacurium               and was diagnosed            PACU.
60      PEDIATRIC    ANESTHESIA          PAPPAS  ET AL.                                                                                 ANESTH      ANALG
        DEXAMETHASONE,         CHILDREN,      AND ADENOTONSILLECTOMY                                                                         1998;87:57-61

Table 2. Frequency of Recovery Characteristics                             in the           indicate that, in children undergoing ambulatory tonsil-
Early and Late Recovery Periods                                                             lectomy, a large single dose (1 mg/kg, maximal dose
                                                          Steroid           Control         25 mg) of IV dexamethasone administered at the induc-
                                                                                            tion of anesthesia decreased PONV and improved oral
                                                           group             group
                                                         (n = 63)          (n = 65)         intake during the first 24-h period after discharge. Ad-
     Early (PACU)                                                                           ditionally, significantly fewer of these children sought
        Fentanyl administered                                 62             66             medical attention with respect to postoperative phone
        Retching/vomiting                                     38             29             calls to a physician, and none returned to the hospital for
        Rescue antiemetic                                     22             18             the management of PONV and/or poor oral intake. Of
        Two rescue antiemetics                                 6             10             note, this beneficial effect of dexamethasone was not
        Good to excellent oral intake                         84             77             evident during early recovery (PACU stay).
     Late (Discharge to 24 h)
        Retching/vomiting                                     24             62*                In a prospective, randomized, double-blind study,
        Rescue antiemetic                                      3             10             Volk et al. (16) observed no differences in postopera-
        Good to excellent oral intake                         83             58”            tive recovery variables, such as oral intake, level of
        Return to hospital for PONV                            0              8*            activity, and analgesic use, in children who received a
           and hydration                                                                    single dose of dexamethasone 10 mg IV versus pla-
        Frequency of phone calls                                8            25”            cebo, although they did not specifically examine
     Total                                                                                  PONV. Catlin and Grimes (15) examined the incidence
        Overall PONV                                          48             88*
        Overall rescue antiemetics                            25             28             of vomiting in addition to pain, fever, and oral intake
                                                                                            in 25 children (4-12 yr of a e) who received placebo or
    Values  are expressed     as %.                                                                                       8
    PACU    = postanesthesia         care unit,   PONV   = postoperative     nausea   and
                                                                                            dexamethasone (8 mg/m ) IV before tonsillectomy.
vomiting.                                                                                   The only difference they observed was in return to a
    * P < 0.05 versus     the steroid    group.                                             full diet, which was faster after dexamethasone. These
                                                                                            studies were published in the otolaryngology litera-
                                                                                            ture and were not standardized for anesthetic and
Discussion                                                                                  perioperative factors.
Although the safety of tonsillectomy and adenotonsil-                                           In the anesthesia literature, Splinter and Roberts
lectomy as outpatient surgical procedures is well doc-                                      (18) described the effect of dexamethasone on postton-
umented, the outpatient setting has not been univer-                                        sillectomy nausea and vomiting. All confounding
sally adopted (2-4). There is also no consensus about                                       perioperative factors were controlled except anesthetic
the time for which these children must be observed                                          induction: more patients in the dexamethasone group
after surgery to ensure a safe discharge with minimal                                       received propofol induction (50% vs 40%). Unlike the
risk of postdischarge complications (4,6). The three                                        present study, a decreased incidence of nausea and
most common postdischarge complications that re-                                            vomiting in dexamethasone-treated children was ob-
quire the children to return to the hospital after am-                                      served both during early (PACU) recovery and de-
bulatory tonsillectomy are hemorrhage, persistent                                           layed (24-h) recovery. Because an IV induction with
PONV, and poor oral intake (5,6,8).                                                         propofol reduces PONV during early recovery, we
                                                                                            speculate that the lower incidence of PONV reported
   To minimize PONV and improve oral intake, anes-
thesiologists have focused primarily on anesthetic                                          during early recovery may be related to the greater
                                                                                            frequency of propofol use in dexamethasone-treated
techniques with minimal emetic potential and on the
administration of different antiemetic drugs (8-12).
                                                                                                The efficacy of dexamethasone in minimizing late
Surgeons, however, have promoted the use of cortico-
                                                                                            PONV in this study and several other published stud-
steroids (methylprednisolone and dexamethasone) to
                                                                                            ies is consistent with its biological half-life of 36-48 h.
minimize morbidity related to postsurgical edema and                                        A prolonged antiemetic effect has also been demon-
inflammation, such as poor oral intake, pain, and fever                                     strated when dexamethasone was used to control
(13,15,16). The efficacy of dexamethasone as an anti-                                       chemotherapy-induced nausea and vomiting (17). The
emetic has been well established in chemotherapy-                                           dose of IV dexamethasone used in the present study
induced nausea and vomiting (17), but studies of its                                        (1 mg/kg, maximal dose 25 mg) was larger than that
antiemetic potential in children undergoing tonsillec-                                      reported in previous studies of patients undergoing
tomy have produced conflicting results (11,15,16,18).                                       tonsillectomy (15,16,18). This dose range has been rec-
   PONV is a multifactorial problem, and several anes-                                      ommended for airway obstruction (19). Complications
thetic and nonanesthetic factors must be standardized to                                    from corticosteroid therapy are typically related to its
examine the antiemetic potential of any specific drug. In                                   long-term use, and risks of steroid therapy of <24-h
the present study, the anesthetic technique, amount of IV                                   duration are negligible (20).
hydration, narcotic analgesic dose, and antiemetic ther-                                        The preoperative administration of a single large
apy were standardized. Data from the present study                                          dose of IV dexamethasone significantly decreased the
ANESTH       ANALG                                                                                                            PEDIATRIC         ANESTHESIA       PAPPAS              ET AL.          61
1998B7t57-61                                                                                    DEXAMETHASONE,                CHILDREN,          AND ADENOTONSILLECTOMY

overall incidence of PONV, specifically          during the                                      7. Crysdale       WS, Russel D. Complications                         of tonsillectomy            and
                                                                                                    adenoidectomy           in 9409 children             observed        overnight.       Can Med
24 h after discharge in children undergoing          ambula-
                                                                                                    Assoc J 1986;135:1139-42.
tory adenotonsillectomy      and tonsillectomy.   Preopera-                                      8. Litman RS, Wu CL, Catanzaro                       FA. Ondansetron             decreases eme-
tive dexamethasone        administration     also improved                                          sis after tonsillectomy                  in children.          Anesth        Analg       1994;78:
postoperative     oral intake, reduced the number           of                                      478-81.
                                                                                                 9. Furst SR, Rodarte               A. Prophylactic             antiemetic       treatment        with
phone calls from parents, and prevented hospital re-
                                                                                                    ondansetron         in children           undergoing         tonsillectomy.          Anesthesi-
turns for the management         of PONV and poor oral                                              ology 1994;81:799-803.
intake during the 24 h after discharge. These beneficial                                        10. Ferrari LR, Donlon JV. Metoclopramide                           reduces the incidence             of
effects of dexamethasone,     however,     were not evident                                         vomiting      after tonsillectomy              in children.       Anesth Analg 1992;75:
during early recovery. We speculate that an antiemetic
                                                                                                11. Ved SA, Walden             TL, Montana             J, et al. Vomiting            and recovery
drug in addition to dexamethasone            may minimize                                           after outpatient         tonsillectomy            and adenoidectomy                in children:
early PONV in these children. Further controlled stud-                                              comparison         of four anesthetic              techniques         using nitrous         oxide
ies, however,   are necessary to verify this practice.                                              with halothane          and propofol.             Anesthesiology           1996;85:4-10.
                                                                                                12. Pandit      UA, Malviya             S, Lewis IH. Vomiting                   after outpatient
                                                                                                    tonsillectomy        and adenoidectomy                in children:        the role of nitrous
The authors are grateful  to Dr. Stephen Slogoff (Chairman,      Depart-                            oxide. Anesth Analg 1995;80:230-3.
ment of Anesthesiology,    Loyola University   Medical   Center)   for his                      13. Tom LWC, Templeton                   JJ, Thomson         ME, et al. Dexamethasone                 in
invaluable  help and advice in the preparation    of this manuscript.                               adenotonsillectomy.                Int J Pediatr            Otorhinolaryngol             1996;37:
                                                                                                14. Anderson       HA, Rice BJ, Cantrell                 RW. Effects of injected               depos-
                                                                                                    teroid on post tonsillectomy                     morbidity:        a double-blind          study.
                                                                                                    Arch Otolarygnol              1975;101:86-8.
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