Use of ketorolac tromethamine in children undergoing scoliosis surgery:an analysis of complications

The Spine Journal 3 (2003) 55–62

1529-9430/03/$ – see front matter © 2003 Elsevier Science Inc. All rights reserved.PII: S1529-9430(02)00446-1

Use of ketorolac tromethamine in children undergoing scoliosis surgery: an analysis of complications

Michael G. Vitale, MD, MPH

a,c

*, Julie C. Choe, MPH

a

, Matthew W. Hwang, MD, MPH

b

,

Rebecca M. Bauer, MPH

b

, Joshua E. Hyman, MD

c

, Francis Y. Lee, MD, PhD

c

,David P. Roye, Jr., MD

c

a

International Center for Health Outcomes and Innovative Research, College of Physicians and Surgeons, and the Josepth L. MailmanSchool of Public Health, Columbia University and New York Presbyterian Hospital, 600 West 168th Street, 7th Floor, New York, NY 10032, USA

b

Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA

c

Division of Pediatric Orthopedics, Department of Orthopedic Surgery, Columbia University College of Physicians and Surgeons, 3959 Broadway, 8th Floor North, New York, NY 10032, USA

Received 1 March 2002; accepted 20 May 2002

Abstract

Background context:

Ketorolac Tromethamine (ketorolac) is a nonsteroidal anti-inflammatorydrug (NSAID) with proven efficacy in decreasing postoperative pain in various surgical settings, in-cluding the treatment of spine deformities. However, some studies have raised questions regardingthe potential side effects of this agent, such as increased bleeding and inhibition of bony fusion.

Purpose:

This study was conducted to determine whether there is any association between the use ofketorolac and postoperative complications in a group of children who underwent scoliosis surgery.

Study design/setting:

This is a retrospective review of a group of children who underwent spinal fu-sion between 1989 to 1999 at our institution.

Patient sample:

Data on a total of 208 children were analyzed in this study. Sixty received ketorolacand 148 did not.

Outcome measures:

Postoperative transfusion and reoperation rates were the two main outcomemeasures of interest.

Methods:

A retrospective review of 208 children who underwent scoliosis surgery was conducted,with a focus on ketorolac use. Univariate analysis and logistic regression were used to quantify thedeterminants of postoperative complications.

Results:

Our analyses detected no significant differences in a broad range of socioclinical variablesbetween the two patient groups, including age at surgery, gender, type of scoliosis, surgical ap-proach, use of erythropoietin, levels of curvature and degree of curvature. Analysis of complicationrates focusing on postoperative transfusion and revision surgery showed that there were no signifi-cant differences between the two groups.

Conclusions:

In this retrospective study of 208 children undergoing spine surgery, postoperative useof ketorolac did not significantly increase complications, including transfusion and reoperation. © 2003Elsevier Science Inc. All rights reserved.

Keywords:

Ketorolac tromethamine; Ketorolac; NSAID; Scoliosis; Children; Complications; Side effects; Transfusion;

Revision surgery

Introduction

Ketorolac tromethamine (brand name Toradol

®

, is a reg-istered trademark of Roche Hoffman-LaRoche Inc., 340Kingsland Street, Nutley, NJ 07110, USA) is a member ofthe nonsteroidal anti-inflammatory drug (NSAID) class andis a potent analgesic commonly used for short-term man-agement of postoperative pain. Tissue damage, such as fromthe trauma of a surgical procedure, causes the local release

FDA device/drug status: Approved for this indication (ketorolactromethamine).

Nothing of value received from a commercial entity related to thisresearch.

* Corresponding author. 600 West 168th Street, 7th Floor, New York,NY 10032, USA. Tel.: (212) 305-5028; fax: (212) 305-4256.

E-mail address: [email protected] (M.G. Vitale)

56

M.G. Vitale et al. / The Spine Journal 3 (2003) 55–62

of a number of chemical mediators of pain and inflamma-tion, including prostaglandins, leukotrienes, bradykinin,histamine, nitric oxide and norepinephrine, that sensitizenearby nociceptors, which results in the subjective sensationof pain [1,2]. Pharmacotherapeutic agents for pain manage-ment often target one of these many mechanisms, and rarelyis one agent sufficient for effective control of pain in thepostoperative setting. Ketorolac, like other NSAIDs, inhib-its the enzyme cyclo-oxygenase (COX). COX convertsarachidonic acid to cyclic endoperoxides, which are the un-stable precursors of prostaglandins, prostacyclin and throm-boxane. One mechanism of NSAID efficacy for analgesia isthought to be this inhibition of local production of prostag-landins, but NSAIDs may have central nervous system ef-fects as well.

Ketorolac does not share the adverse effects of opioids,which can include respiratory depression, nausea and vom-iting, sedation, gastrointestinal stasis, urinary retention andthe potential for abuse. This side effect profile makes ketor-olac use particularly appealing for postoperative pain man-agement in children. Ketorolac is an effective alternativeadjuvant to morphine during general anesthesia in pediatricsurgery [3]. Ketorolac also reduces opioid requirementswithout increased incidence of bleeding and decreasedlength of hospital stay after tonsillectomies [4,5] and effec-tively controls pain and reduces opioid requirements, aswell as the length of hospital stay, in children who have un-dergone ureteroneocystostomies [6,7]. In a prospective, ran-domized, double-blind study, ketorolac was comparable tomorphine for postoperative pain relief in children [8]. Ke-torolac also significantly decreases opioid requirements forpostoperative pain relief in children [9].

The efficacy of ketorolac in postoperative pain manage-ment and reducing narcotic requirements in pediatric surgi-cal populations also applies to pediatric orthopedic patients.In the context of a prospective, randomized, double-blindstudy, Vetter and Heiner [10] demonstrated that a single in-traoperative dose of ketorolac to children undergoing vari-ous orthopedic surgical procedures decreases the necessarydose of opioids by means of patient-controlled analgesia andprovides better pain control than patient-controlled analgesiaalone. Children in this study also experienced decreased fre-quency of urinary retention secondary to opioid use in thefirst 12 hours after surgery. Sutters et al. [11] compared theuse of postoperative morphine patient-controlled analgesiawith and without multiple doses of ketorolac by children whohad undergone major orthopedic procedures in a prospective,randomized, double-blind, placebo-controlled study. The au-thors found that the group of children who had receivedketorolac required significantly less opioids, used patient-controlled analgesia less, had lower pain intensity ratingsand experienced less narcotic-associated side effects, suchas nausea, pruritus and urinary retention. A case-controlstudy conducted by Eberson, et al. [12] compared ketorolacversus morphine in a postoperative pediatric orthopedic set-ting and found that the ketorolac group required signifi-

cantly fewer doses of morphine, had fewer gastrointestinalside effects and shorter hospital stays.

Despite these documented benefits of ketorolac for paincontrol, the drug has many potential side effects, includingplatelet function impairment (secondary to the inhibition ofthe formation of thromboxane A2), gastrointestinal bleedingand perforation and renal impairment [13]. Studies examin-ing children who have undergone various surgical procedures,such as myringotomy, strabismus correction and reconstruc-tive and orthopedic procedures, have reported no increasedrisk of bleeding complications. However, ketorolac use in ton-sillectomies is controversial because of increased bleedingrisk, although its use in this case would be a particularly valu-able method of postoperative pain management and avoidingnarcotic-associated complications, such as airway obstructionand nausea and vomiting [14,15].

The effects of ketorolac, and NSAIDs in general, onbone metabolism and healing are very controversial and areclearly of particular interest when considering their use inorthopedic patients. The evidence has been conflicting. Onestudy examining the effect of the NSAID ibuprofen on frac-ture healing in adult rats revealed no differences in the rateof bone remodeling and formation in rats [16], whereas an-other study presented evidence of an adverse effect on bonehealing in rabbits [17]. Ketorolac has been shown to have adose-dependent inhibitory effect on bone repair in adult rab-bits [18]. The inhibitory effects of ketorolac on endochon-dral ossification were confirmed radiologically in the sec-ond to fourth week of fracture healing in rabbits [19].However, ketorolac was found to have no significant ad-verse effect on healing within the first 3 days after osteot-omy in rats when compared with indomethacin and saline[20]. Animal studies specifically studying the effects ofNSAIDs on spinal fusion have shown inhibitory effects aswell: indomethacin interferes with spinal fusion in adult rats[21], and ketorolac has been shown to have an inhibitory ef-fect on spinal fusion in adult rabbits [22].

Postoperative ketorolac administration in human adultspine surgery patients also has received mixed reviews thusfar. Ketorolac is an effective adjunct to patient-controlledmorphine, resulting in decreased morphine use and somno-lence and better analgesia [23]. In addition, smaller doses ofketorolac are as effective as larger doses in patients whohave had spine stabilization surgery [24]. However, a retro-spective study of ketorolac in adult spine surgical patientsrevealed that patients who received ketorolac were fivetimes more likely than patients who did not to result in non-union (odds ratio [OR]

�

5.0) [25]. These studies have gen-erated an appropriate caution regarding ketorolac use in theearly postoperative period of spine patients. However, thepotential benefits of superior analgesia as well as the de-creased need for narcotics warrant further investigation ofrisk versus benefit of ketorolac use in the pediatric spine pa-tient.

There are several strategies commonly used to decreasethe postoperative pain associated with the surgical treatment


57

of scoliosis in children, including the use of ketorolac. As inadults, ketorolac use in children raises concerns about in-creased risk of bleeding and inhibition of bony fusion. Todate, few studies have examined clinical outcomes of pedi-atric patients undergoing major orthopedic procedures andreceiving ketorolac for postoperative pain relief. Althoughempirical evidence suggests that side effects of ketorolacwould be less pertinent in a pediatric population, these is-sues have not been specifically examined in children. Be-cause of the great potential benefit of ketorolac use in the pe-diatric surgical population, especially in orthopedic patients,we examined the incidence of postoperative complicationsand their association with ketorolac use in children who un-derwent surgery for scoliosis. Although a retrospective studydesign poses various sources of bias, we believe it is a logicalfirst step toward a better understanding of issues in this area.

Materials and methods

Data

A retrospective study of hospital medical records wasconducted on 208 patients who underwent scoliosis surgeryat our institution from 1989 to 1999. Over this time period,some but not all patients were treated with ketorolac as partof their routine postoperative pain management. Of thesepatients, 60 children had received ketorolac postoperatively,whereas the remaining 148 children did not. Ketorolac wasgenerally used as a salvage medication when inadequatepain control or complications arose while using narcotics.The decision to use ketorolac was not randomized but ratherwas made on clinical grounds on a case-by-case basis by thesenior author. Furthermore, any child with known allergiesto opioids or those who experience nausea, itching or poorpain control on maximum dose of opioids were given ketor-olac instead. The average dose of ketorolac administeredwas 0.5 mg/kg, given intravenously every 6 hours, for 2 to 3days, starting 24 to 28 hours after surgery.

Information regarding socioclinical variables, includingage, gender, diagnosis, surgical approach, erythropoietin treat-ment, reoperation, postoperative hematocrit level, length ofstay, length of follow-up, postoperative gastrointestinal com-plications, level of curvature and degree of curvature, was col-lected on all 208 patients. The endpoints of interest involvedtwo types of complications: 1) increased risk of bleeding, asrepresented by the need for transfusion, and 2) revision sur-gery because of pseudarthrosis, infected hardware or hardwarefailure. It should be noted that although we are interested inthe effect of ketorolac on nonunion, other reasons for reopera-tion, such as infection or decompensation, were also included.

Analysis

Univariate analyses were performed to quantify the num-ber of patients in each socioclinical category. Table 1 illus-trates the demographic and clinical profile of our patientpopulation.

Bivariate analyses were conducted between the two end-points of interest (or dependent variables)—the need for trans-fusion and reoperation—and the various socioclinical variablescollected on each study patient. Tables 2 and 3 show the resultsof the crude OR method of comparison for transfusion and re-operation, respectively. The results of the final logistic regres-sion analysis are shown in Table 4 and 5. For each of these ta-bles, the same seven independent variables were entered intothe regression model: ketorolac treatment, erythropoietin treat-ment, diagnosis (type of scoliosis), surgical approach, length ofstay, level of curvature and degree of curvature.

Results

Descriptive data

Table 1 illustrates the demographic and clinical charac-teristics of our patient population, stratified by postopera-

Table 1Demographic and clinical characteristics of ketorolac versus nonketorolac patients

Ketorolac(n

�

60) %

No ketorolac(n

�

148)%

GenderMale 21.7 31.8Female 78.3 68.2

DiagnosisIdiopathic scoliosis 55.0 45.9Neurogenic scoliosis 33.3 27.0Congenital scoliosis 8.3 18.9Kyphosis 1.7 3.4Other 1.7 4.7

Surgical approachPosterior 56.7 48.6Anterior 13.3 13.5Combined 30.0 37.8

Erythropoietin treatmentNo 46.7 52.3Yes 53.3 47.7

ReoperationNo 86.7 87.1Yes 13.3 12.9

Type of reoperationNonunion 37.5 52.6Infection 25.0 36.8Decompensation 37.5 10.5

Gastrointestinal problems*No 86.7 93.2Yes 13.3 6.8

TransfusionNo 73.3 78.4Yes 26.7 21.6

Level of curvature (mean

�

SD) 9.8

�

3.5 9.1

�

4.2Degree of curvature (mean

�

SD) 65.7

�

22.7 58.4

�

19.7Hematocrit level

†

(mean

�

SD) 28.8

�

5.9 28.7

�

5.2Length of stay (mean

�

SD) 10.1

�

10.8 8.0

�

5.2Length of follow-up (mean

�

SD) 61.7

�

23.3 68.7

�

31.1Age at surgery (mean

�

SD) 13.5

�

2.5 13.3

�

4.3

*Postoperative gastrointestinal complications.

†

Postoperative hematocrit level.

58


tive ketorolac treatment. Of the 208 patients in this study,60 (29%) were identified as having been treated with ketor-olac, whereas 148 (71%) did not receive this drug. Theoverall patient population was predominantly female, withan average age at surgery of 13.4 years (range, 1.8 to 28.6).Approximately half of the children in each patient groupwere diagnosed with idiopathic scoliosis and about anotherthird with neurogenic scoliosis. The number of levels of spi-nal curvature involved was similar in the two groups, butthe degree of curvature was higher among ketorolac-treatedpatients, with an average curvature of 66 degrees (range, 26to 130 degrees) versus an average of 58 degrees (range, 28to 110 degrees) among non–ketorolac-treated patients.

More than half (53%) of those who received ketorolacwere also treated with erythropoietin, whereas less than half(47%) received this drug in the nonketorolac group. Themean postoperative hematocrit level was similar in the twopatient groups. The posterior approach was most widely

conducted among these patients. However, the averagelength of stay was lower in the nonketorolac group with amean of 8.0 days (range, 1 to 39 days), compared with 10.1days (range, 4 to 62 days) in the ketorolac group. The lengthof follow-up was longer in patients who did not receive ke-torolac, with a mean of 68.71 months (range, 17.54 to124.06), compared with 61.67 months (range, 16.69 to98.10) in children who did not receive this drug. Slightlymore patients treated with ketorolac (27%) needed to betransfused, compared with patients in the nonketorolacgroup (22%), but this was not statistically significant. Dur-ing this time, approximately 13% in each patient group un-derwent some type of revision surgery.

Bivariate analysis

The crude ORs for transfusion and reoperation are shownin Tables 2 and 3, respectively. The reference group for eachindependent variable was chosen at random and assigned an

Table 2The odds of transfusion (crude odds ratio)

Transfusion(n

�

48)No transfusion(n

�

160)Crude oddsratio

95% Confidenceinterval p value

KetorolacNo 32 116 1.00 — —Yes 16 44 1.32 0.66–2.64 .44

GenderMale 17 43 1.00 — —Female 31 117 0.67 0.34–1.33 .25

DiagnosisIdiopathic scoliosis 12 89 1.00 — —Neurogenic scoliosis 28 32 5.60 2.80–11.20 .0001Congenital scoliosis 7 26 0.88 0.36–2.18 .78Kyphosis 0 6 NA* NA* NA*Other 1 7 0.47 0.06–3.88 .48

Surgical approachAnterior 7 21 1.00 — —Posterior 18 88 0.49 0.25–0.95 .04Combined 23 51 1.97 1.02–3.79 .04

Erythropoietin treatmentNo 26 51 1.00 — —Yes 12 63 0.37 0.17–0.81 .013

ReoperationNo 41 139 1.00 — —Yes 6 21 0.97 0.59–1.58 .91

Gastrointestinal problems

†

No 43 145 1.00 — —Yes 4 14 0.97 0.55–1.74 .93

Hematocrit level

‡

— — 0.98 0.92–1.04 .45Level of curvature

§

— — 1.12 1.02–1.22 .02Degree of curvature

�

— — 1.05 1.03–1.07 .0001Length of stay

¶

— — 1.07 1.02–1.12 .006Age at surgery

#

— — 1.003 0.92–1.09 .95Length of follow-up** — — 0.99 0.87–1.13 .89

*None of the kyphosis cases underwent a transfusion.

†

Postoperative gastrointestinal complications.

‡

Postoperative hematocrit level; estimate for each additional unit increase in hematocrit level.

§

Estimate for each additional level of increase in curvature involvement.

�

Estimate for each additional degree increase in curvature.

¶

Estimate for each additional day in hospital.

#

Estimate for each additional year increase in age.**Estimate for each additional month of follow-up.


59

OR of 1.00. For instance, in Table 2, the reference group fordiagnosis was patients with idiopathic scoliosis. Other typesof diagnoses (neurogenic, congenital, kyphosis, other) werecompared with the idiopathic cases separately. In Table 2, sixindependent variables were determined to be significant inpredicting transfusion: diagnosis (neurogenic scoliosis cases),surgical approach (both posterior and combined methods),levels of curvature, degree of curvature, length of stay in thehospital after surgery and erythropoietin treatment. More spe-cifically, neurogenic cases were more than five times aslikely to undergo a transfusion than idiopathic cases (crudeOR

�

5.6, 95% confidence interval [CI]

�

2.8 to 11.2). Levelof curvature involved (crude OR

�

1.12/level, 95% CI

�

1.02to 1.22) was also a significant predictor of transfusion. Simi-larly, degree of curvature, estimated for each degree, was asignificant independent factor (crude OR

�

1.05/degree, 95%CI

�

1.03 to 1.07). In terms of surgical approach, the posteriorapproach was protective against transfusions in comparison

to the anterior approach (crude OR

�

0.49, 95% CI

�

0.25 to0.950). On the other hand, patients who underwent a com-bined anterior-posterior approach were almost twice as likelyto receive a transfusion compared with those who underwentonly an anterior approach (crude OR

�

1.97, 95% CI

�

1.02 to3.79). Erythropoietin was a protective factor against transfu-sion in our study, with about 70% less likely to require atransfusion (crude OR

�

0.37, 95% CI

�

0.17 to 0.81). Finally,transfusion led to a longer stay in the hospital in this setting(crude OR

�

1.07, 95% CI

�

1.02 to 1.12).In determining the likelihood for reoperation, as shown

in Table 3, only one independent variable was found to besignificant: degree of curvature. Degree of curvature wassignificant in predicting reoperation, without adjusting forany other variables (crude OR

�

1.03, 95% CI

�

1.004 to1.05). Treatment with ketorolac was not a significant inde-pendent predictor for either transfusion or reoperation in ourpatient population.

Table 3The odds of reoperation (crude odds ratio)

Reoperation(n

�

27)No reoperation(n

�

180)Crudeodds ratio

95% Confidence interval p value

KetorolacNo 19 128 1.00 — —Yes 8 52 1.04 0.43–2.52 .94

GenderMale 10 49 1.00 — —Female 17 131 0.64 0.27–1.48 .29

DiagnosisIdiopathic scoliosis 8 93 1.00 — —Neurogenic scoliosis 10 49 1.57 0.67–3.67 .29Congenital scoliosis 7 26 2.07 0.80–5.39 .13Kyphosis 1 5 1.35 0.15–11.98 .79Other 1 7 0.95 0.11–8.04 .96

Surgical approachAnterior 6 22 1.00 — —Posterior 14 92 1.03 0.46–2.31 .94Combined 7 66 0.61 0.24–1.51 .28

Erythropoietin treatmentNo 7 70 1.00 — —Yes 13 62 2.10 0.79–5.59 .14

Gastrointestinal problems*No 23 165 1.00 — —Yes 3 15 1.17 0.61–2.26 .63

TransfusionNo 21 139 1.00 — —Yes 6 41 0.97 0.37–2.56 .95

Hematocrit level

†

— — 1.02 0.94–1.10 .71Level of curvature

‡

— — 1.04 0.93–1.16 .50Degree of curvature

§

— — 1.03 1.004–1.05 .02Length of stay

�

— — 1.04 0.99–1.08 .10Age at surgery

¶

— — 0.98 0.88–1.09 .70Length of follow-up

#

— — 0.99 0.85–1.17 .94

*Postoperative gastrointestinal complications.

†

Postoperative hematocrit level; estimate for each additional unit increase in hematocrit level.

‡


§


�

Estimate for each additional day in hospital.

¶

Estimate for each additional year increase in age.

#

Estimate for each additional month of follow-up.

60


Multivariate analysis

Multivariate analyses were conducted in order to adjustfor possible confounding and/or interaction effects amongthe many independent variables in this study. In Table 4,the six factors that were significant for transfusion from thecrude analysis in Table 2 were included in the final logisticregression model. Given that ketorolac is the main factor ofinterest in this study, this seventh variable was also enteredinto the final model for transfusion. According to this ad-justed analysis, degree of curvature (adjusted OR

�

1.03,95% CI

�

1.004 to 1.06) remained as the only significantvariable predicting transfusion, even after adjusting for con-founding and interaction. Ketorolac treatment did not affectthe rate of transfusion.

In Table 3, only a single independent variable was signif-icant in predicting reoperation:degree of curvature. How-ever, the same seven factors from Table 4 were entered intothe final logistic regression model for reoperation in Table5. Again, ketorolac treatment did not significantly influencethe need for reoperation, even after adjusting for other vari-ables in the model.

Discussion

The primary goal of this study was to evaluate the potentialinhibitory effects of systemic ketorolac on spine fusions, aswell as the potential postoperative bleeding complications in apediatric population. To our knowledge, this is the largeststudy to date examining the complications of administering ke-torolac postoperatively in children undergoing spine surgery.

Although we recognize the limits of a retrospective study,we thought that our study was a rational first step toward a de-

finitive answer to the question of the safety of ketorolac use inpediatric spine surgery patients. As mentioned earlier, the deci-sion to administer ketorolac postoperatively was made by thesenior author on a case-by-case basis. The decision was madebased on the child’s known allergies to opioids, nausea, itch-ing, poor pain control, somnolence and respiratory depression.Although the children who received ketorolac constituted themore difficult cases in our study, thus limiting the generaliz-ability of the study, we did not find a significantly increasedrate of complications in these patients. Ideally, a randomizedcontrolled trial will shed further light on the subject.

Based on the known potential complications secondaryto ketorolac use, we chose postoperative transfusion and re-operation rates as our two main measures of interest. Wechose transfusion, because we thought that it was a reason-able indicator of bleeding that we could measure accuratelyin a retrospective fashion. Also, the decision to transfuse apatient was based on the senior author’s assessment ofbleeding complications. Therefore, we thought that postop-erative transfusion would serve well as a proxy for such.Reoperation rates captured those patients who had to un-dergo a revision surgery for pseudarthrosis, infected hard-ware or hardware failure. We specifically analyzed the datafor pseudarthrosis rates as an indicator for risk of inhibitionof bony fusion and found that there was no significant dif-ference between the two patient groups. One potential majorlimitation of this endpoint as an indicator for nonunion isthe length of postoperative follow-up. Our average length offollow-up was almost 62 months for children who receivedketorolac and 69 months for those who did not. We thoughtthat this was acceptable, given both the decreased likelihoodof children compared with adults to experience nonunionand the retrospective nature of the study.

Table 4Final logistic regression model for transfusion

Adjustedodds ratio

95% Confidence interval p value

KetorolacNo 1.00 — —Yes 1.06 0.40–2.78 .91

Erythropoietin treatmentNo 1.00 — —Yes 0.52 0.21–1.30 .16

DiagnosisIdiopathic scoliosis 1.00 — —Neurogenic scoliosis 2.71 0.94–7.83 .07Congenital scoliosis 3.67 0.92–14.60 .06

Surgical approachAnterior 1.00 — —Posterior 1.30 0.29–5.73 .73Combined 1.27 0.27–5.99 .76

Length of stay* 1.03 0.98–1.10 .22Level of curvature

†

1.11 0.97–1.26 .13Degree of curvature

‡

1.03 1.004–1.06 .02

*Estimate for each additional day in hospital.

†


‡


Table 5Final logistic regression model for reoperation

VariableAdjustedodds ratio

95% Confidenceinterval p value

KetorolacNo 1.00 — —Yes 0.99 0.32–3.10 .99

Erythropoietin treatmentNo 1.00 — —Yes 3.79 1.17–12.27 .03

DiagnosisIdiopathic scoliosis 1.00 — —Neurogenic scoliosis 1.34 0.34–5.30 .68Congenital scoliosis 1.27 0.22–7.27 .79

Surgical approachAnterior 1.00 — —Posterior 0.45 0.09–2.19 .32Combined 0.62 0.13–3.09 .56

Length of stay* 1.02 0.96–1.07 .55Level of curvature

†

0.99 0.84–1.17 .94Degree of curvature

‡

1.02 0.99–1.06 .21

*Estimate for each additional day in hospital.

†


‡



61

Although the use of ketorolac was not randomized in thisstudy, our analysis detected no significant differences in abroad range of socioclinical variables. Our data revealed aslightly larger proportion of children who received ketoro-lac did require transfusion; however, the difference was notstatistically significant. We also found no difference in theincidence of revision surgery between the two patientgroups. However, degree of curvature was a significant pre-dictor for transfusion, whereas erythropoietin treatment wasa significant predictor for reoperation in this study accord-ing to the final regression models for these two endpoints,respectively. These are concerning endpoints, but given thatthe decision to treat with ketorolac was not randomized, andthat the patient population who received ketorolac was com-posed primarily of complicated patients, we think that ourconclusions about the safety of ketorolac use in this popula-tion are valid. A larger, randomized controlled study willprovide insight into these endpoints. Overall, these datasuggest that postoperative use of ketorolac in children withscoliosis surgery does not significantly increase bleedingand nonunion complications, but a larger population isneeded to exclude definitively any association.

The results from our retrospective study indicate that fur-ther research into the use of ketorolac in the pediatric ortho-pedic surgical patient population is warranted. Animal stud-ies that have examined the effects of ketorolac on bonehealing have largely been conducted using adult animals.One possible solution is to study the effects of systemic ke-torolac administration on spine fusion or long bone fracturehealing using adolescent animal models. By quantifying theinhibitory effect of ketorolac on bone healing in immatureanimals, we can clarify further the appropriateness of ketor-olac use in pediatric orthopedic patients.

Conclusions

Our retrospective study indicates that the use of ketoro-lac for postoperative pain management does not increaserisk of bleeding complications or reoperation in a group ofchildren who underwent spine surgery. On the other hand,the degree of preoperative curvature seems to be a signifi-cant determinant of transfusion risk. Several other interest-ing findings were noted in this study. As found in previousstudies, children with neurogenic scoliosis tend to have asignificantly greater risk of transfusion, as do children withlarger curves. Based on the results of our retrospectivestudy, use of ketorolac did not seem to increase this risk,even in these groups of patients.

Our next logical step in clinical investigation is the initia-tion of a prospective, randomized, double-blind, multicenterstudy, which will allow us to determine definitively whetherketorolac has clinically significant inhibitory effects onspine fusion in children. Included in this follow-up clinicalstudy would be an examination of the commonly acceptedeffects of ketorolac, potential positive and negative patientoutcomes, as well as the potential savings incurred from de-

creased incidence of opioid-induced side effects. However,this study provides evidence to support our current use ofketorolac as an adjunct to postoperative pain managementin patients after spine surgery, and we continue to use thismedication routinely.

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One Hundred Years Agoin Spine . . .

The 1903 Nobel Prize for Physics wasawarded to Antoine Becquerel (1852–1908), Marie Curie(1867–1934) and Pierre Curie (1859–1906). Marie Curiewon a second Nobel Prize, for Chemistry, in 1911. They

isolated radium from the study of pitchblend, a materialrich in uranium and thorium, and showed it to be ex-tremely radioactive.

References

[1] Becquerel AH. Sur les radiations émisesparphosphorescence. CRAcad Sci (Paris) 1896;10:420–1.

[2] Curie P, Curie MS. Sur une substance nouvelle radio-active, con-tinue dans la pitchblend. CR Acad Sci (Paris) 1898;127:175–8,1215–7.

David Fardon

Knoxville, TN

Use of ketorolac tromethamine in children undergoing scoliosis surgery:an analysis of complications

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