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Intrathecal morphine for analgesia in children undergoing selective dorsal rhizotomy
‘188’. Jouinal
ojPaifl and Symptom h4ana,qmmt
Vol. 11 No. 3 b@ch
1996
Intrathecal Morphine for’ Analgesia in Children Undergoing Selective Dorsal -Rhizotomy
Address qbrintsqustr tarTeresa E. Dews, MD, Department of General Anesthesiology, Cleveland Clinic Foundation, 9500 Euclid Avenue M26, Cleveland, OH 44195, USA. Abstract presented at the 67th Congress Of the lnternationzd Anesthesia Research Society, San Diego, California, March 18-23, 1993. Current affiliation of Arno Fried, MD, is Department of Pediatric Neurosurgery, Rhode Island Hospital/Brown University, Providence, RI. Current aflibation pf Kenneth Ozw&t, MD, is Pain Management Center, Cape Fear Valley Hospital, Fayette, NC. Acc$k?dfmpublication: July 20, 1995, 08853924/96/~15.00 SSDI 0&?5-3924(95)0016&9
spastic dipiegia is a form of cerebral palsy characterized by spasticity and muscle weakness that primarily or exclusively &ecrs the lower extremities. It afflicts the. majority of patients with cerebral palsy and is associated with permanent motor disabilities.’ Because spastic dipiegia can cause significant disability, complicate nursing care. and limit activities of daily living, several management techniques have been devised. Currently, antispastic medications, physical therapy, orthopedic operations, and selective dorsal root rhizotomy (SDRR) are used for management.’ Selective dorsal root rhizotomy involves a partial deafferentation of the lumbosacrai dorsal roots. Therefore, it reduces spasticity by diminishing the number of afferent signals to the circuits involving the spinal stretch reflex, Benefits include permanent reduction ofspasticik and improvement in the pattern of gait and in the ability to perform daily activities.rS’S9*‘o It may reduce the likelihood of future orthopedic operations, and there is no sensory disturbance despite the deafferentalion.‘-” One of the most difficult +spects of management in patients undergoing SDRR is the presence of substantial postoperative pain, muscle spasm, and dysesthesias.28” This p;& may be the result of the extensive sl;rgical exposure with multiple laminectomies and nerve root manipulation.’ Innathecal morphine is knowrI to provide up to 24 hr of postoperative pain relief for various surgical procedures.“,4,‘~‘“,‘~ At our institution, it is rr+tinely. administered intraoperatively at durai closure after dorsal root rhizotomy. As only lir”.ited observations have been made Gth respect to the efficacy of intrathecal morphine in these patients,s we sought to define an optimal dose of intrathecal morp,bine in children having SDRR through a randomized, double-blind prospeciive trial.
M&OdS Aft&r institutional appr?val and parental written informed consent, 2’7 patientswere randomized to receive 10, 20, or 50 pg-kg-’ (Groups A, B, .and C, respectively) of preservative-free ‘morphine ir.&hecally. All
pascnts ages Z-10 years with a history of cerebral palsy and spastic diplegia schedule8 for selective dorsal root rhizotomy performed between November 1, 1990, through Novcm6~ 1, 1992, were ‘Quded. Those u;ith severe rc:@tory disease c 7” ! chronic exposure .A!sensitivity to opioids were excluded (one patient). Anesthesia consisted of induction with thioiental and/or haIotbane, short- or intermediate-acting neuromuscular blockade, and isoihnane for mainrenatice. Ventilation was conrrolled LO maintain end-tidal PCO, at 25-35 mm Hg. All patients had indwelling urinary catheters. Phor to incision, the skin was infiltrated with 5-10 mL 0.5% lidocaiue with epinephrine 1:200,000. The p&en& underwent bilateral LlSl laminectomiei with identification of the motor and sensory roots and sebaraation of the sensory (dorsal) rootlets. Once separated, the dorsal roodets were individually stimulated using proximal &d distal nerve stimulators. Under electromyographic gpidance, nerve rootlets exhibiting continuous muscle contraction were sectioned. At least two nerve rootlets were left at each level. The dut-a was then sutured closed. Absence of cerebral spinal fluid leakage w& evaluated by direct observation of the dural incision while the anesthetist performed a Vaisalva maneuver tith, positive pressure ventilation. If no le& were observed, preservative-free morphine War administered by the surgeon ,via a 25-gauge needle. Morphine has piepared by the pharmacy in a manner that utilized di!ution with preservative-free normal saline and did not allow r:-ryyirinn of the dose. The volume of solutian Injected was adjusted for weight (see Table 1). No other s.ys!er+ opioid ?r sedar$e medication was admrnlstered preOpf%IliVdy or intraoperatively. Patients were exrubated in the operating room suite within 2 hr of the intrathecal morphine doe<:. Postopemtiveiy, +al signs, pulse oximetry, observer visual analogue scale (VAS), and Children’s Hospital of Eastern Ontario Pain Scale (CHEOPS)” were recorded every houi for 24 hr in a pedidttic intensive care step down unit. Anchors for the VAS v&e “no pain” = O.and “most stiere pain possible” = ‘IO. The range of total score on the CHEWS 64-13. The nursing staff r&eived t@dng on the use of both scales.
Thbbl Dose Table
Patient weight
(kg)
Dose Group
10.00-13.32
0.10 0.13
16.66-19.98 19.99-23.31 23.32-26.64 26.65-29.97 29.9b33.30 33.31-36.63 36.64-39.96 e-9.97
0.17
13:3’*16.65 __._~ ~~__
fur Intitl&cai
A (mg)
Mor+ine
Dose Group
0.20 0.23 0.27
0.30, 0.33 0.37 0.40
in Dorsal
R (mg)
0.20 0.27 0.33 0.40 : 0.47 0.53 0.60 0.67 0.73. 0.80
Rhizotomy
Dose c.r~up C (mg)
Total Vo. Inj. ([FL)
0.30
0.30 0.40 0.50 0.60 0.70 (I.80
0.10
0.50 0.60 0.70 0.80 a.90 1.at-l 1.10 1.20
0.90 1.00 1.10 1.20
dure for Kruskal-Wallis analyses. For the categorical data, the three groups were compared using Fisher’s exact test. Friedman’s test was used to examine the changes over time (total cumulative dose, VAS all,1 CHEOPS scores), as at some time points the data values for each of the three factors were not normally distrib uted. If the change over time was significant (P < 0.05), then multipIe pair-wise comparisons were performed using the paired 1 test or Wilcoxon signed-rank tests, as appropriate. Thg Bonferroni method ivas used to adjust the significance level for multiple comparisons.
The duration of analgesia ,was judged to be the time interval between intrathrcal morphine administration and the first intravenous (IV) morphine dose. Alsd noted was the cumulative dose of supplemental IV morphine, which was administered according LO VAS in a standardized fashion. Nurses were ‘instructed to administer morphine intravenously every hour pet tbe folIowing schedule: VAS O-4, no treatment; VAS 5-7, give 0.05 pgkg-’ Iv; and VAS S-10, give 0.1 pKkg-’ IV. They were then to,re-eYaluate the patient’s VAS after 15 min and repeat intravenous ‘.administration up to one additional d&e per hour’according to the above scale for VAS scores. The nurses assessed muscle spasm separately and requested specific orders from the surgical team as needed. The occurrences of postop erative pruritus, ,hemodynamic instability, respiratory depression (respiratory rate 110, and/oi SaO,592), nausea and vomiting’were recorded. All observers were unaware of the dose of intratbecai morphine; For ihe continuous demographic factors, analysis of variance (ANOVA) or KruskalWallis test was’ used, as appropriate, to compare the groups. If the overall results were significant, multiple Comparisons were performed using the Tukey method for ar.alysis of variance {ANOVA), bnci the Dunn ;:roce-
The groups were’equivalent,with Irespect ,to gender,,age, .weight, and height (s&e Table.2). There was considerable individual variability in the duration of analgesia arid cumulative supplemental morphine doses: Time to tint suppltimental morphine dose was not statistically d’ifferent among groups (242 r 173, 188 2 153 min, and 395 2 344 min, respectively, for Group A, B, and’ C) (see Table 3). The cumulative supplemental morphine dose at 6, 12, and 18 hr was significantly lower in Group C than in Group B. At 6 hr, it,w+s also sign& candy lower than in Group A (see Table 3). By 24 hr, cumulative supplemetital morphinrTable 2
Supplemental
T&k 3 lb&p&e
Riqukement
Time to first IV MSO, dose (mean t SD) Group
A (N=,S) B (N- 9) C (N=
8j
IV, i~imwnons:
IT MSO, disc
min
10 pgkg-l 20 pgkg-’ 30 pgkkg-’
St; ; ;;; 395
Cumulative Group
r 344
A (N= 9)’ B (H=9) c (N= 9)
dose @g-kg. -t mean % SD)
6hr.
12 hr
f9.12 74 189.6?126
196.8-t109 424.9~200# 160 f:25
38.61
47’
18 hr 362 618
ltlt56 +-272k
307.3Z-185
24hr 5092229 713t288 505t341
MS<>,, morpldrie sulfsw
‘P-C 0.05 yenl~ A atid 0: tw <,a.05 v~fi!l~ A ;~nd c.
dose was equivalettt in all three groups. Two patients (one each in Groups A and C) received an intravenous dose (0.5 mgkg-‘) of diazepam during the observation period for lower extremity muscle spasm. The incidence of respiratory depression, nausea and vomiting, or pruritus, did not differ between groups (see Table 4). One child each in Groups A and B developed oxygen saturation = 90, and an additional two patients had desaturation to 86%-88% (one each in Groups A and C)..These patients had resolution of hypoxia spontaneously (A), with supplemental 0, (C), or incentive spirometry/intermittent positive pressure breathing (one each in,Groups A and B). The onset of the respiiatory events was variable (range, 1-24 br). Hemodynamic instability or apnea requiring naloxone therapy did not occur. Pain scores did not differ between groups preopemtivefy, at tbe time of first intravenous morphine dose, or in the ‘postoperative observation period (Figure ? and Figure 2).
lliwusion SDjRR is thought to be ‘a procedure associated with significant postoperative pain.‘*” in the past, management has cons/sted of’multiple intravenous doses of opioids with ensuing side effects of sedation and respiratory depression. In addition, analgesia was often inadequate as assessed by postoperative mobility and ability to participate in physical therapy.’ The use of opioids iu the central axis has been described for .a variety of surgical procedures and has been shown to protide a,prolonged (E-48 hr) duration of postoperative analgesia. y.4.7’ Although the administration of epidural and intrathecal ,morphine has been reported in patients undergoing SDRR.s*” This
trial
is the only prospective dose-response to evaluate both duration of analgesia and supplemental opioid requirement. Although the duration of analgesia in our study (range, 1-15 hr) was much shorter than that of Harris et al. (3-48 hr),s they also reported a high degree of individual variability in the duration of analgesia after intrathecal morphine and no clear dose response. Variability may result from large inter-individual variati0.n in morphine cerebrospinal fluid (CSF) kinetics”‘~‘” or from leakage of ititratbecal contents (CSF and morphine) through either rhe dural closure or the puncture left by tbe 25gauge needle used to administer morphine.. A leak that was significant enough to affect .our results is feasible even if it was not obvious during the procedure. The shorter duration of analgesia may be due to differences in criteria for administration of supplemental IV analgesic or to differences in the dilution of the iutntbecai morphine applied. in cantrasr to previous investigations, we evaluated the supplemental morphine requirement as well as the duration of analgesia. We were utta’.*le to observe a graded dosedependrme ofanalgesia ($te 20 pgkg-’ dose was less effective than the 10 Pgkg-’ dose). The unexpected results in the 20 pgkg-’ group warrant further consideration. With the exception of two out of the nine patients in this group, all Group B patients required supplemental morphine, earlier and at higher
study
T&k4
W.
0 PREOP
1
6
12
18
II
No. 3
Marrhi996
24
Hours fig. 1. Mean VAS pain scores during the first 24 postoperative hours, grouped by ITMS dose. Since the data were not normally distributed at certain tilne points, standard deviations are omitted.
of intrathecal morphine alone. Patients in a control group would have received analgesic medication only after’they were evahtated in the recovery room. This may have resulted in severe pain in some patients therefore, an intrathecal placebo was not thought to, be a humane option. Side effects experienced by the patients in this study were similar to that observed in other studiesz4 Although there was no statistical +f: ference among groups, the small number of patients may have precluded a demonstration of differences in side ,effects. .Unlikc the study of Jones et a1,,4 there W.S no clear pattern lo the
doses than patients in Group A. This discrepat-q is puzzling, but it may be related to the small number of patients in each group and to the marked inter-individual variability of the data. Group B did have a higher percentage of female patients, but there is no evidence in the literature that gender affects sensitivity to spinal opioids. The dilution of the intiathecal morphine was rechecked and found accurate. A placebo group may have provided addi’ tional insight in this regard. However, the study protocol- precluded the use of preoperative or intraopetative opioids or sedatives so that analgesia would be referable to the a&on Rg. 2. Mean CHEOPS were not mxma!ly
Pain scores during
dktriottted
at,cetuin
the first 24 posroptrative time points,
stahdard
CHEOPS
:j 1..
hours, deviations
SCORE
_‘_ _-. . _:_ _ _ _ _ “” “. . . _ ” _ _ _ _ _ _ _ _ _ _ _.
07 PREOP
grouped by ITMS are omitted.
*.
/ 1
6
12 Wours
1s
24
dose. Since the data
respiratory depression in our observations. Similady, we could find no association between the respiratory depression and the administration of intravenous morphine. Although the +satumtion was easily treated with conservative measures, its presence underlines the need for close monitoring of respiratory status in the postop’ erative period, Neither subjective nor objective. pain scores differed among the groups, possibly reflecting equivalence in quality of analgesia provided by the protocol. The choice of the parameters for the sliding scale for IV morphine administmtion was based on the experience at our ins& tution. A VAS of 4 or less is considered adequate analgesia in adult postoperative patients. Further study is needed to validate this method in children. Although cognitive development was not documented for each patient, self-report may be difficult in this population because of age ,or developmental delay. Therefore, a behavioral observational scale was also used in addition to the observer VAS to assess patients’ pain. The CHZQPSs is a behavioral rating scale developed to assess pediatric postoperative pain in the recovery room. It has been shown to be less reliable in the extended perioperative period.” .Because it ‘is based on clearly defined behaviors, this pain scaIe has the potential to eliminate 01 reduce observer bias and was therefore thought to be attractive for use in the current study.. Furthermore, .observer VAS was chosen as an alternate pain scale because it is used frequently in the special care unit in which the children were evaluated, and it has been studied and shown to correlate highly with CHEOPS.” Although this was not specifically revzlidited in our study, the behavior of the VAS score appeared to mimic (or parallel) that of the CHEOPS score (see Figures 1 and 2). Our observation that postoperative pain scores did not differ among groups may have been due to either a lack crf sensitivity on the part of the pain assessment scale or the fact Grat analgesia wa.s equivalent because of the use’of a standardized protocol for administra tion of additional mdrphine. The frequent reevaluation of-the ‘patient’s pain status may have served to equalize the level of pain among groups. The use of diazepam was minimal and reflected that postoperative muscle
spasm in the ini& 24 hr was not a contributing factor in our study Cur results indicate that an intrathecal morphine dose of 30 pg-kg-’ may provide better pain relief than either LO or 20 pgkg-’ for the first 6 hr after gDRR and 20 pg-kg-’ was definitely the least effective dose. The lowest dose, 10 pgkg?’ may be ‘effective provided an increased’anafgesic requirement i anticipated in the first 6 hr.postopetativeiy Frequent observer assessment of pain and the use of a sliding s&e for pain medications provided good suppiemental analgesia. Further study to develop and vaiidate pain assessment tools in patients with cerebral palsy and spasticity who are undergoing major surgical procedures is needed.
1. Park TS, Owen J. Surgical management of spastic diplegia in cerebral palsy. N Engf J Med 1992; 326745-749. 2. Sparkes ML, Klein 45. Use of epidurat marphine for control of postoperative pain in selective dorsal rhizotomy for spasticity. Pediarr Neurosci 1989;15:229-232. 3. Tobias J. Deshpande J, Dubaime’ A, et al. Use of intrathecal morphine in ‘children’. Clio Pediatr (Phila) 199&29:44-48: 4. Jones SEE- Beasiey JM. Macfarlane DWR, D&s $4, Hall-Dades G. lntrathecal morphine for postop omtive pain relief in children. BrJ Anaestb 1984;56: 137-140. 5. Harris t%, Kahana M, Park TS. Intrathecal morphine fdr postoperative analgesia in children aBeer selective doma1 root rhizotomy. Neurosurgery 1991; 28~519-522. 6. McGrath FJ, Johnson C, Goodman J, &hillinger J+ Dunn J: ChapmanJ. CHEOPS a behavioral scale for rating postoperative pain in children. In: Fields HLI Dubner 8, eds. Advances in p&r research and therapy, ~0’. 9. New York: Raven, 1985: 395402. 7. Nordberg G, Hedner T, Mellstmnd T, Dalstrom B. Pbarmacokinedc aspects of intratbecal morphine analgesia. Anesthesiology 1984;60%8-454. 8. Landau MW, Hunr CC. Dona! rbizotomy, a treatment of unproven efficacy J Child Neurnl 1990;5%174-178. 9. Gaskill SJ, Wilkins K, Marlin AE. S&ctive pastenor rbizotomy to treat spasticity. zusociated tirb cere bml pa@ a critical review. Tex Med ~!M?;88~6&71. 10. Peacock %, Staudt W. Spastidty in cerebra!paby and the selotctive posterior rhizotomy procedure.J Child Nemo1 199f);5:179185.
194
Dpws et al.
11. Sjostrom S, Taams~v A, Pers.son P, Hartvig P. Pharmacokinetics of intrathecal morphine and meperidine in humans. Anesthesiology 1987;67: $w3Y5. 12. Ross D, Drasner K, Weinstein P, .Flaherty J, Barbara N. Use of. intrathecally administered morphine in the treatment of postoperative pain after lumbar spinal surgery: a prospective, double-blind, placebo-controlled study Neurosurgery ~991:28:700-704.
Vol. 811 h’o. 3 March
19%
13. Y&h T. Spinal opiate analgesia: characteristics and principles of action. Pain 1981;11:29.3-346. 14. Berde C, Beyer.J, Bourn&i M, L&n C, Scthna N. Comparison of morphine and methadone or prevention of posrbpeutive pain in 3-7 year old children. J Pediatr 1991;119:136-141.. 15. Jacobson L, Chabal. C, Brcdy. .4 dose-response study af intrathecal morphine: efficacy, duraeion, optimal dose, and side effects. Anesth Analg 1988; 63:1082--1088.
ojPaifl and Symptom h4ana,qmmt
Vol. 11 No. 3 b@ch
1996
Intrathecal Morphine for’ Analgesia in Children Undergoing Selective Dorsal -Rhizotomy
Address qbrintsqustr tarTeresa E. Dews, MD, Department of General Anesthesiology, Cleveland Clinic Foundation, 9500 Euclid Avenue M26, Cleveland, OH 44195, USA. Abstract presented at the 67th Congress Of the lnternationzd Anesthesia Research Society, San Diego, California, March 18-23, 1993. Current affiliation of Arno Fried, MD, is Department of Pediatric Neurosurgery, Rhode Island Hospital/Brown University, Providence, RI. Current aflibation pf Kenneth Ozw&t, MD, is Pain Management Center, Cape Fear Valley Hospital, Fayette, NC. Acc$k?dfmpublication: July 20, 1995, 08853924/96/~15.00 SSDI 0&?5-3924(95)0016&9
spastic dipiegia is a form of cerebral palsy characterized by spasticity and muscle weakness that primarily or exclusively &ecrs the lower extremities. It afflicts the. majority of patients with cerebral palsy and is associated with permanent motor disabilities.’ Because spastic dipiegia can cause significant disability, complicate nursing care. and limit activities of daily living, several management techniques have been devised. Currently, antispastic medications, physical therapy, orthopedic operations, and selective dorsal root rhizotomy (SDRR) are used for management.’ Selective dorsal root rhizotomy involves a partial deafferentation of the lumbosacrai dorsal roots. Therefore, it reduces spasticity by diminishing the number of afferent signals to the circuits involving the spinal stretch reflex, Benefits include permanent reduction ofspasticik and improvement in the pattern of gait and in the ability to perform daily activities.rS’S9*‘o It may reduce the likelihood of future orthopedic operations, and there is no sensory disturbance despite the deafferentalion.‘-” One of the most difficult +spects of management in patients undergoing SDRR is the presence of substantial postoperative pain, muscle spasm, and dysesthesias.28” This p;& may be the result of the extensive sl;rgical exposure with multiple laminectomies and nerve root manipulation.’ Innathecal morphine is knowrI to provide up to 24 hr of postoperative pain relief for various surgical procedures.“,4,‘~‘“,‘~ At our institution, it is rr+tinely. administered intraoperatively at durai closure after dorsal root rhizotomy. As only lir”.ited observations have been made Gth respect to the efficacy of intrathecal morphine in these patients,s we sought to define an optimal dose of intrathecal morp,bine in children having SDRR through a randomized, double-blind prospeciive trial.
M&OdS Aft&r institutional appr?val and parental written informed consent, 2’7 patientswere randomized to receive 10, 20, or 50 pg-kg-’ (Groups A, B, .and C, respectively) of preservative-free ‘morphine ir.&hecally. All
pascnts ages Z-10 years with a history of cerebral palsy and spastic diplegia schedule8 for selective dorsal root rhizotomy performed between November 1, 1990, through Novcm6~ 1, 1992, were ‘Quded. Those u;ith severe rc:@tory disease c 7” ! chronic exposure .A!sensitivity to opioids were excluded (one patient). Anesthesia consisted of induction with thioiental and/or haIotbane, short- or intermediate-acting neuromuscular blockade, and isoihnane for mainrenatice. Ventilation was conrrolled LO maintain end-tidal PCO, at 25-35 mm Hg. All patients had indwelling urinary catheters. Phor to incision, the skin was infiltrated with 5-10 mL 0.5% lidocaiue with epinephrine 1:200,000. The p&en& underwent bilateral LlSl laminectomiei with identification of the motor and sensory roots and sebaraation of the sensory (dorsal) rootlets. Once separated, the dorsal roodets were individually stimulated using proximal &d distal nerve stimulators. Under electromyographic gpidance, nerve rootlets exhibiting continuous muscle contraction were sectioned. At least two nerve rootlets were left at each level. The dut-a was then sutured closed. Absence of cerebral spinal fluid leakage w& evaluated by direct observation of the dural incision while the anesthetist performed a Vaisalva maneuver tith, positive pressure ventilation. If no le& were observed, preservative-free morphine War administered by the surgeon ,via a 25-gauge needle. Morphine has piepared by the pharmacy in a manner that utilized di!ution with preservative-free normal saline and did not allow r:-ryyirinn of the dose. The volume of solutian Injected was adjusted for weight (see Table 1). No other s.ys!er+ opioid ?r sedar$e medication was admrnlstered preOpf%IliVdy or intraoperatively. Patients were exrubated in the operating room suite within 2 hr of the intrathecal morphine doe<:. Postopemtiveiy, +al signs, pulse oximetry, observer visual analogue scale (VAS), and Children’s Hospital of Eastern Ontario Pain Scale (CHEOPS)” were recorded every houi for 24 hr in a pedidttic intensive care step down unit. Anchors for the VAS v&e “no pain” = O.and “most stiere pain possible” = ‘IO. The range of total score on the CHEWS 64-13. The nursing staff r&eived t@dng on the use of both scales.
Thbbl Dose Table
Patient weight
(kg)
Dose Group
10.00-13.32
0.10 0.13
16.66-19.98 19.99-23.31 23.32-26.64 26.65-29.97 29.9b33.30 33.31-36.63 36.64-39.96 e-9.97
0.17
13:3’*16.65 __._~ ~~__
fur Intitl&cai
A (mg)
Mor+ine
Dose Group
0.20 0.23 0.27
0.30, 0.33 0.37 0.40
in Dorsal
R (mg)
0.20 0.27 0.33 0.40 : 0.47 0.53 0.60 0.67 0.73. 0.80
Rhizotomy
Dose c.r~up C (mg)
Total Vo. Inj. ([FL)
0.30
0.30 0.40 0.50 0.60 0.70 (I.80
0.10
0.50 0.60 0.70 0.80 a.90 1.at-l 1.10 1.20
0.90 1.00 1.10 1.20
dure for Kruskal-Wallis analyses. For the categorical data, the three groups were compared using Fisher’s exact test. Friedman’s test was used to examine the changes over time (total cumulative dose, VAS all,1 CHEOPS scores), as at some time points the data values for each of the three factors were not normally distrib uted. If the change over time was significant (P < 0.05), then multipIe pair-wise comparisons were performed using the paired 1 test or Wilcoxon signed-rank tests, as appropriate. Thg Bonferroni method ivas used to adjust the significance level for multiple comparisons.
The duration of analgesia ,was judged to be the time interval between intrathrcal morphine administration and the first intravenous (IV) morphine dose. Alsd noted was the cumulative dose of supplemental IV morphine, which was administered according LO VAS in a standardized fashion. Nurses were ‘instructed to administer morphine intravenously every hour pet tbe folIowing schedule: VAS O-4, no treatment; VAS 5-7, give 0.05 pgkg-’ Iv; and VAS S-10, give 0.1 pKkg-’ IV. They were then to,re-eYaluate the patient’s VAS after 15 min and repeat intravenous ‘.administration up to one additional d&e per hour’according to the above scale for VAS scores. The nurses assessed muscle spasm separately and requested specific orders from the surgical team as needed. The occurrences of postop erative pruritus, ,hemodynamic instability, respiratory depression (respiratory rate 110, and/oi SaO,592), nausea and vomiting’were recorded. All observers were unaware of the dose of intratbecai morphine; For ihe continuous demographic factors, analysis of variance (ANOVA) or KruskalWallis test was’ used, as appropriate, to compare the groups. If the overall results were significant, multiple Comparisons were performed using the Tukey method for ar.alysis of variance {ANOVA), bnci the Dunn ;:roce-
The groups were’equivalent,with Irespect ,to gender,,age, .weight, and height (s&e Table.2). There was considerable individual variability in the duration of analgesia arid cumulative supplemental morphine doses: Time to tint suppltimental morphine dose was not statistically d’ifferent among groups (242 r 173, 188 2 153 min, and 395 2 344 min, respectively, for Group A, B, and’ C) (see Table 3). The cumulative supplemental morphine dose at 6, 12, and 18 hr was significantly lower in Group C than in Group B. At 6 hr, it,w+s also sign& candy lower than in Group A (see Table 3). By 24 hr, cumulative supplemetital morphinrTable 2
Supplemental
T&k 3 lb&p&e
Riqukement
Time to first IV MSO, dose (mean t SD) Group
A (N=,S) B (N- 9) C (N=
8j
IV, i~imwnons:
IT MSO, disc
min
10 pgkg-l 20 pgkg-’ 30 pgkkg-’
St; ; ;;; 395
Cumulative Group
r 344
A (N= 9)’ B (H=9) c (N= 9)
dose @g-kg. -t mean % SD)
6hr.
12 hr
f9.12 74 189.6?126
196.8-t109 424.9~200# 160 f:25
38.61
47’
18 hr 362 618
ltlt56 +-272k
307.3Z-185
24hr 5092229 713t288 505t341
MS<>,, morpldrie sulfsw
‘P-C 0.05 yenl~ A atid 0: tw <,a.05 v~fi!l~ A ;~nd c.
dose was equivalettt in all three groups. Two patients (one each in Groups A and C) received an intravenous dose (0.5 mgkg-‘) of diazepam during the observation period for lower extremity muscle spasm. The incidence of respiratory depression, nausea and vomiting, or pruritus, did not differ between groups (see Table 4). One child each in Groups A and B developed oxygen saturation = 90, and an additional two patients had desaturation to 86%-88% (one each in Groups A and C)..These patients had resolution of hypoxia spontaneously (A), with supplemental 0, (C), or incentive spirometry/intermittent positive pressure breathing (one each in,Groups A and B). The onset of the respiiatory events was variable (range, 1-24 br). Hemodynamic instability or apnea requiring naloxone therapy did not occur. Pain scores did not differ between groups preopemtivefy, at tbe time of first intravenous morphine dose, or in the ‘postoperative observation period (Figure ? and Figure 2).
lliwusion SDjRR is thought to be ‘a procedure associated with significant postoperative pain.‘*” in the past, management has cons/sted of’multiple intravenous doses of opioids with ensuing side effects of sedation and respiratory depression. In addition, analgesia was often inadequate as assessed by postoperative mobility and ability to participate in physical therapy.’ The use of opioids iu the central axis has been described for .a variety of surgical procedures and has been shown to protide a,prolonged (E-48 hr) duration of postoperative analgesia. y.4.7’ Although the administration of epidural and intrathecal ,morphine has been reported in patients undergoing SDRR.s*” This
trial
is the only prospective dose-response to evaluate both duration of analgesia and supplemental opioid requirement. Although the duration of analgesia in our study (range, 1-15 hr) was much shorter than that of Harris et al. (3-48 hr),s they also reported a high degree of individual variability in the duration of analgesia after intrathecal morphine and no clear dose response. Variability may result from large inter-individual variati0.n in morphine cerebrospinal fluid (CSF) kinetics”‘~‘” or from leakage of ititratbecal contents (CSF and morphine) through either rhe dural closure or the puncture left by tbe 25gauge needle used to administer morphine.. A leak that was significant enough to affect .our results is feasible even if it was not obvious during the procedure. The shorter duration of analgesia may be due to differences in criteria for administration of supplemental IV analgesic or to differences in the dilution of the iutntbecai morphine applied. in cantrasr to previous investigations, we evaluated the supplemental morphine requirement as well as the duration of analgesia. We were utta’.*le to observe a graded dosedependrme ofanalgesia ($te 20 pgkg-’ dose was less effective than the 10 Pgkg-’ dose). The unexpected results in the 20 pgkg-’ group warrant further consideration. With the exception of two out of the nine patients in this group, all Group B patients required supplemental morphine, earlier and at higher
study
T&k4
W.
0 PREOP
1
6
12
18
II
No. 3
Marrhi996
24
Hours fig. 1. Mean VAS pain scores during the first 24 postoperative hours, grouped by ITMS dose. Since the data were not normally distributed at certain tilne points, standard deviations are omitted.
of intrathecal morphine alone. Patients in a control group would have received analgesic medication only after’they were evahtated in the recovery room. This may have resulted in severe pain in some patients therefore, an intrathecal placebo was not thought to, be a humane option. Side effects experienced by the patients in this study were similar to that observed in other studiesz4 Although there was no statistical +f: ference among groups, the small number of patients may have precluded a demonstration of differences in side ,effects. .Unlikc the study of Jones et a1,,4 there W.S no clear pattern lo the
doses than patients in Group A. This discrepat-q is puzzling, but it may be related to the small number of patients in each group and to the marked inter-individual variability of the data. Group B did have a higher percentage of female patients, but there is no evidence in the literature that gender affects sensitivity to spinal opioids. The dilution of the intiathecal morphine was rechecked and found accurate. A placebo group may have provided addi’ tional insight in this regard. However, the study protocol- precluded the use of preoperative or intraopetative opioids or sedatives so that analgesia would be referable to the a&on Rg. 2. Mean CHEOPS were not mxma!ly
Pain scores during
dktriottted
at,cetuin
the first 24 posroptrative time points,
stahdard
CHEOPS
:j 1..
hours, deviations
SCORE
_‘_ _-. . _:_ _ _ _ _ “” “. . . _ ” _ _ _ _ _ _ _ _ _ _ _.
07 PREOP
grouped by ITMS are omitted.
*.
/ 1
6
12 Wours
1s
24
dose. Since the data
respiratory depression in our observations. Similady, we could find no association between the respiratory depression and the administration of intravenous morphine. Although the +satumtion was easily treated with conservative measures, its presence underlines the need for close monitoring of respiratory status in the postop’ erative period, Neither subjective nor objective. pain scores differed among the groups, possibly reflecting equivalence in quality of analgesia provided by the protocol. The choice of the parameters for the sliding scale for IV morphine administmtion was based on the experience at our ins& tution. A VAS of 4 or less is considered adequate analgesia in adult postoperative patients. Further study is needed to validate this method in children. Although cognitive development was not documented for each patient, self-report may be difficult in this population because of age ,or developmental delay. Therefore, a behavioral observational scale was also used in addition to the observer VAS to assess patients’ pain. The CHZQPSs is a behavioral rating scale developed to assess pediatric postoperative pain in the recovery room. It has been shown to be less reliable in the extended perioperative period.” .Because it ‘is based on clearly defined behaviors, this pain scaIe has the potential to eliminate 01 reduce observer bias and was therefore thought to be attractive for use in the current study.. Furthermore, .observer VAS was chosen as an alternate pain scale because it is used frequently in the special care unit in which the children were evaluated, and it has been studied and shown to correlate highly with CHEOPS.” Although this was not specifically revzlidited in our study, the behavior of the VAS score appeared to mimic (or parallel) that of the CHEOPS score (see Figures 1 and 2). Our observation that postoperative pain scores did not differ among groups may have been due to either a lack crf sensitivity on the part of the pain assessment scale or the fact Grat analgesia wa.s equivalent because of the use’of a standardized protocol for administra tion of additional mdrphine. The frequent reevaluation of-the ‘patient’s pain status may have served to equalize the level of pain among groups. The use of diazepam was minimal and reflected that postoperative muscle
spasm in the ini& 24 hr was not a contributing factor in our study Cur results indicate that an intrathecal morphine dose of 30 pg-kg-’ may provide better pain relief than either LO or 20 pgkg-’ for the first 6 hr after gDRR and 20 pg-kg-’ was definitely the least effective dose. The lowest dose, 10 pgkg?’ may be ‘effective provided an increased’anafgesic requirement i anticipated in the first 6 hr.postopetativeiy Frequent observer assessment of pain and the use of a sliding s&e for pain medications provided good suppiemental analgesia. Further study to develop and vaiidate pain assessment tools in patients with cerebral palsy and spasticity who are undergoing major surgical procedures is needed.
1. Park TS, Owen J. Surgical management of spastic diplegia in cerebral palsy. N Engf J Med 1992; 326745-749. 2. Sparkes ML, Klein 45. Use of epidurat marphine for control of postoperative pain in selective dorsal rhizotomy for spasticity. Pediarr Neurosci 1989;15:229-232. 3. Tobias J. Deshpande J, Dubaime’ A, et al. Use of intrathecal morphine in ‘children’. Clio Pediatr (Phila) 199&29:44-48: 4. Jones SEE- Beasiey JM. Macfarlane DWR, D&s $4, Hall-Dades G. lntrathecal morphine for postop omtive pain relief in children. BrJ Anaestb 1984;56: 137-140. 5. Harris t%, Kahana M, Park TS. Intrathecal morphine fdr postoperative analgesia in children aBeer selective doma1 root rhizotomy. Neurosurgery 1991; 28~519-522. 6. McGrath FJ, Johnson C, Goodman J, &hillinger J+ Dunn J: ChapmanJ. CHEOPS a behavioral scale for rating postoperative pain in children. In: Fields HLI Dubner 8, eds. Advances in p&r research and therapy, ~0’. 9. New York: Raven, 1985: 395402. 7. Nordberg G, Hedner T, Mellstmnd T, Dalstrom B. Pbarmacokinedc aspects of intratbecal morphine analgesia. Anesthesiology 1984;60%8-454. 8. Landau MW, Hunr CC. Dona! rbizotomy, a treatment of unproven efficacy J Child Neurnl 1990;5%174-178. 9. Gaskill SJ, Wilkins K, Marlin AE. S&ctive pastenor rbizotomy to treat spasticity. zusociated tirb cere bml pa@ a critical review. Tex Med ~!M?;88~6&71. 10. Peacock %, Staudt W. Spastidty in cerebra!paby and the selotctive posterior rhizotomy procedure.J Child Nemo1 199f);5:179185.
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11. Sjostrom S, Taams~v A, Pers.son P, Hartvig P. Pharmacokinetics of intrathecal morphine and meperidine in humans. Anesthesiology 1987;67: $w3Y5. 12. Ross D, Drasner K, Weinstein P, .Flaherty J, Barbara N. Use of. intrathecally administered morphine in the treatment of postoperative pain after lumbar spinal surgery: a prospective, double-blind, placebo-controlled study Neurosurgery ~991:28:700-704.
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13. Y&h T. Spinal opiate analgesia: characteristics and principles of action. Pain 1981;11:29.3-346. 14. Berde C, Beyer.J, Bourn&i M, L&n C, Scthna N. Comparison of morphine and methadone or prevention of posrbpeutive pain in 3-7 year old children. J Pediatr 1991;119:136-141.. 15. Jacobson L, Chabal. C, Brcdy. .4 dose-response study af intrathecal morphine: efficacy, duraeion, optimal dose, and side effects. Anesth Analg 1988; 63:1082--1088.