The mean time to first opioid rescue was 22.4 ± 16.9 h (range: 0–48 h, 95% CI: 19.9–24.8 h) (Fig. 2), while the mean time to first IV ketorolac rescue was 35 ± 18 h (range: 0–48 h, 95% CI: 32.4–37.5 h).
Four patients received IV morphine within 12 h of IT morphine injection, as the other rescue medications did not control the pain adequately. Two patients received morphine by IV patient-controlled analgesia devices (PCA) starting at 6 and 10 h, respectively after the administration of IT morphine. One of these two patients had undergone a nephrectomy; the other underwent thoracoscopy. The pain management service directly supervised the PCA administration and a baseline infusion of morphine was avoided in these two patients.
Intraoperative opioids were used in 130 patients (70%). Fentanyl (1–2 mcg/kg) was administered to 105 (56%) patients, morphine (50–100 mcg/kg) to 22 (12%) patients, and remifentanil infusion (0.1–1 mcg·kg−1· min−1) was used in three (2%) patients. The mean time to first opioid rescue in these patients was 20.1 ± 16.7 h when compared with 27.6 ± 16.2 h in those who did not receive intraoperative opioids (P < 0.05). Table 3 shows the list of procedures, the use of intraoperative opioids, and the mean time to first opioid rescue.
The side effect profile is presented in Table 4. In the PACU, vomiting was observed in 19 patients (10%) and 17 received ondansetron, metoclopromide or a combination of metoclopromide, ondansetron, and dexamethasone. On the floor, 60 patients (32%) had symptoms of nausea or vomiting. Twenty-nine patients (16%) received ondansetron, nine (5%) received metoclopromide, and one (0.5%) received both ondansetron and metoclopromide. Seventy patients (37%) had pruritus, and 24 of these (13%) received nalbuphine treatment.
Urinary catheters were placed during the intraoperative period in 106 patients (57%) for surgical reasons (66% of our patients had urological procedures). The remaining 81 patients did not have an indwelling catheter postoperatively. Five of these patients (6%, 95% confidence limits 2.3%–13.8%) were diagnosed to be in urinary retention in the postoperative period, and were managed with a one-time straight catheterization of the bladder.
Three patients had unintended dural puncture with the 19-guage introducer needle. One of them developed symptoms of PDPH on postoperative day 2, which resolved in 24 h with conservative management that included hydration, IV caffeine, and ibuprofen. Supplemental oxygen was administered via nasal canula to two patients (1%) for brief periods in the postoperative period because of hypoxemia (O2 saturation <95%). In these two patients, the episodes occurred at 6 h in one (8 yr old) and at 12 h in the other (4 yr old) after surgery. The episodes were self-limited and no patient received assisted ventilation or naloxone administration. The first patient received fentanyl (1 mcg/kg) intraoperatively, while the other did not receive any intraoperative opioids. However, neither of the above two patients received any supplemental opioid after surgery, before the desaturation episodes. The first patient (desaturation at 6 h) received the first rescue opioid only 18 h after surgery and the second patient (desaturation at 12 h) received the first opioid rescue 28 h after surgery.
This review shows that low-dose IT morphine can provide adequate analgesia in the first 24 h after several types of operations, with 80% of our patients not receiving supplemental rescue opioids in the first 8 h and 52% receiving only oral rescue analgesics in the first 24 h. As this was a retrospective study, we cannot state with certainty that rescue analgesics were always administered when needed. However, we believe that the possibility of inadequate rescue analgesia would be small, as pain in these patients was actively managed by the pain service using a specifically developed protocol. There are clear advantages to an approach where a single intraoperative administration of a drug is accompanied by a minimal requirement for additional interventions for supplemental analgesia in the postoperative period. The rapid transition to the oral route of analgesic therapy has obvious implications in reducing costs and improving patient satisfaction. In contrast, there are increased personnel and equipment costs with alternative analgesic regimens, such as continuous epidural infusions or IV PCA therapy.
There have been studies evaluating the use of IT opioids in the pediatric population, but many were limited to spine and cardiothoracic surgical procedures (8–15) and used doses up to 10–30 mcg/kg of IT morphine (8–10,12,14). We chose a dose of 4–5 mcg/kg based on a previous study (11), where 5 mcg/kg was found be an effective dose balancing potency and side effects in children undergoing spine fusion surgery, a procedure associated with severe postoperative pain.
In our study we noted that the use of intraoperative opioids was associated with a significantly shorter time to first opioid rescue. The most likely reason for this is that intraoperative opioids were more commonly used in more painful surgical procedures. The data in Table 3 seem to support this reasoning.
We observed a relatively low incidence of side effects when compared with previous studies. Many reports in adults demonstrate that IT morphine, although very effective with respect to postoperative analgesia, can cause severe side effects. The incidence of pruritus, emesis, and respiratory depression is dose-dependant and with a reported incidence varying from 60% to 80% for emetic symptoms (16–18), 20%–100% for pruritus (19,20), and 0.36% (21) for respiratory depression. In our study the incidence of side effects was also lower when compared with that reported in other studies where higher doses of IT morphine were used in children (10). In many of these studies, patients received IV opioids via a PCA device in the postoperative period. Hence, it is difficult to establish the exact role of IV PCA and IT morphine in causing the observed side effects. In the only published study in which postoperative analgesia was provided solely by IT morphine (10), the incidence of nausea or vomiting (57%–86%) was significantly higher than that in our report. However, patients in that study received a higher dose of IT morphine than those in our study (10–30 mcg/kg vs 4–5 mcg/kg, respectively).
There are major concerns about the potential for delayed life-threatening respiratory depression after IT morphine administration. The reported incidence of respiratory depression in adult patients who have received an IT opiate is 0.36% (21), but respiratory depression has been variously defined in different studies (22), making it difficult to determine its true incidence even in systematic reviews. In our study no patient developed life-threatening respiratory depression when positive pressure ventilation or naloxone therapy was administered, although two patients did receive supplemental oxygen after the first postoperative hour. As we had 187 patients in our study, we can only state that the upper 95% CI of the incidence of life-threatening respiratory depression after this dose of IT morphine is <3 in 187 (1.6%) (23). We believe that most of these patients can be safely monitored (with well placed protocols) on the regular floor as the incidence of serious side effects, with small dose IT morphine, is low.
Although we used IT morphine in two children less than 6 mo of age, the safety of neuraxial opioids in this age group has not been proven. It may be more prudent to admit these very young patients to a high observation setting such as an intensive care unit until more data are available about the safety of this route of administration. There are data supporting that the ventilatory response to carbon dioxide is depressed for up to 18 h after IT morphine administration in children, but infants do not exhibit greater ventilatory depression than older children (24). The concomitant use of IV opioids increases the risk of serious ventilatory depression (25), reinforcing the need for strict protocols limiting the use of supplemental IV opioids in patients receiving IT morphine.
Most of our patients had a urinary catheter inserted during the intraoperative period as part of the surgical procedure. The incidence of urinary retention was only 6% in patients who did not have a urinary catheter, suggesting that routine urinary catheterization may not be necessary for all patients receiving IT morphine. There was only a single case of PDPH, which probably resulted from the documented wet tap with the introducer needle (19-guage) and resolved with only conservative measures.
We conclude that low-dose IT morphine in the pediatric patient can provide an effective and safe option for postoperative analgesia after many surgical procedures and need not be limited to the cardiothoracic, oncology, or spine surgeries. Additional information is required about the potential for rarer adverse events and protocols must be in place for adequate postoperative monitoring and for limiting the use of IV opioids after IT morphine.
1. Bier A. Experiments regarding cocainization of the spinal cord. Dtsch Z Chir 1899;51:361–9.
2. Wang JK, Nauss LA, Thomas JE. Pain relief by intrathecally applied morphine in man. Anesthesiology 1979;50:149–51.
3. Galloway K, Staats PS, Bowers DC. Intrathecal analgesia for children with cancer via implanted infusion pumps. Med Pediatr Oncol 2000;34:265–7.
4. Meignier M, Ganansia MF, Lejus C, Testa S. Intrathecal morphine therapy in children with cancer. Cah Anesthesiol 1992;40:487–90.
5. Tobias JD, Mateo C, Ferrer MJ, et al. Intrathecal morphine for postoperative analgesia following repair of frontal encephaloceles in children: comparison with intermittent, on-demand dosing of nalbuphine. J Clin Anesth 1997;9:280–4.
6. Merkel SI, Voepel-Lewis T, Shayevitz JR, Malviya S. The FLACC: a behavioral scale for scoring postoperative pain in young children. Pediatr Nurs 1997;23:293–7.
7. Allison PD. Missing data thousand oaks. California, CA: Sage, 2002.
8. Blackman RG, Reynolds J, Shively J. Intrathecal morphine: dosage and efficacy in younger patients for control of postoperative pain following spinal fusion. Orthopedics 1991;14:555–7.
9. Dalens B, Tanguy A. Intrathecal morphine for spinal fusion in children. Spine 1988;13:494–8.
10. Dews TE, Schubert A, Fried A, et al. Intrathecal morphine for analgesia in children undergoing selective dorsal rhizotomy. J Pain Symptom Manage 1996;11:188–94.
11. Gall O, Aubineau JV, Berniere J, et al. Analgesic effect of low-dose intrathecal morphine after spinal fusion in children. Anesthesiology 2001;94:447–52.
12. Goodarzi M. The advantages of intrathecal opioids for spinal fusion in children. Paediatr Anaesth 1998;8:131–4.
13. Hammer GB, Ngo K, Macario A. A retrospective examination of regional plus general anesthesia in children undergoing open heart surgery. Anesth Analg 2000;90:1020–4.
14. Harris MM, Kahana MD, Park TS. Intrathecal morphine for postoperative analgesia in children after selective dorsal root rhizotomy. Neurosurgery 1991;28:519–22.
15. Peterson KL, DeCampli WM, Pike NA, et al. A report of two hundred twenty cases of regional anesthesia in pediatric cardiac surgery. Anesth Analg 2000;90:1014–19.
16. Cardoso MM, Carvalho JC, Amaro AR, et al. Small doses of intrathecal morphine combined with systemic diclofenac for postoperative pain control after cesarean delivery. Anesth Analg 1998;86:538–41.
17. Dahl JB, Jeppesen IS, Jorgensen H, et al. Intraoperative and postoperative analgesic efficacy and adverse effects of intrathecal opioids in patients undergoing cesarean section with spinal anesthesia: a qualitative and quantitative systematic review of randomized controlled trials. Anesthesiology 1999;91:1919–27.
18. Palmer CM, Emerson S, Volgoropolous D, Alves D. Dose-response relationship of intrathecal morphine for postcesarean analgesia. Anesthesiology 1999;90:437–44.
19. Krajnik M, Zylicz Z. Understanding pruritus in systemic disease. J Pain Symptom Manage 2001;21:151–68.
20. Yeh HM, Chen LK, Lin CJ, et al. Prophylactic intravenous ondansetron reduces the incidence of intrathecal morphine-induced pruritus in patients undergoing cesarean delivery. Anesth Analg 2000;91:172–5.
21. Rawal N, Arner S, Gustafsson LL, Allvin R. Present state of extradural and intrathecal opioid analgesia in Sweden. A nationwide follow-up survey. Br J Anaesth 1987;59:791–9.
22. Ko S, Goldstein DH, VanDenKerkhof EG. Definitions of “respiratory depression” with intrathecal morphine postoperative analgesia: a review of the literature. Can J Anaesth 2003;50:679–88.
23. Hanley JA, Lippman-Hand A. If nothing goes wrong, is everything all right? Interpreting zero numerators. JAMA 1983;249:1743–5.
24. Nichols DG, Yaster M, Lynn AM, et al. Disposition and respiratory effects of intrathecal morphine in children. Anesthesiology 1993;79:733–8 (discussion 25A).
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25. Shapiro A, Zohar E, Zaslansky R, et al. The frequency and timing of respiratory depression in 1524 postoperative patients treated with systemic or neuraxial morphine. J Clin Anesth 2005;17:537–42.