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Article Reviews and Commentary

A randomized comparison of ketorolac and morphine for postoperative analgesia in critically ill children.

Lieh-Lai M, Kauffman R, Uy HG et al. Crit Care Med 1999; 27: 2786-2791

This prospective study of 102 patients was designed to evaluate the subsequent morphine use in a variety post operative patients in the ICU given either ketorolac 0.6 mg/kg or morphine 0.1 mg/kg IV as their first analgesic. The two groups were similar in demographics and underwent the various surgeries in similar numbers. Of the twenty-five of the patients who underwent spinal fusions, 15 received ketorolac and 10 morphine. The twenty-four neurosurgical patients were evenly divided between the two groups, as were the 52 cardiovascular patients.

There was not a statistical difference between the two groups regarding analgesia over the 4 hour time period of the investigation. The authors found the groups also did not differ in the following measurements: BUN, Cr, AST, the incidence of hematuria and proteinuria. Bleeding time was also measured and not found to differ between the two groups. The authors also report that none of their patients exhibited abnormal postoperative bleeding or gastrointestinal bleeding.

Ketorolac reduces postoperative narcotic requirements.

Carney DE, Nicolette LA, Ratner MH et al. Journal of Pediatric Surgery 2001; 39: 76-79

The authors review the course of 29 patients given ketorolac, 0.5 mg/kg IV every 6 hours for 8 doses in this case control study. The 29 patients were matched with controls who were given only morphine. Morphine was used as a rescue analgesic in the ketorolac group. The ketorolac group used 0.36 mg/kg/day of morphine compared to the morphine-only group who used 1.08 mg/kg/day. The surgical procedures which the ketorolac group underwent included: perforated (4) and non perforated(6) appendectomies, Nissen fundoplication(8) and a variety of other general surgical procedures. The authors mention in the discussion that there was no alteration in bleeding complications.

Platelet dysfunction after intravenous ketorolac or propacetamol.

Niemi TT, Backman JT, Syrjala MT et al. Acta Anaesthesiol Scand 2000; 44: 69-74

The authors investigated the effects of propacetamol, 60 mg/kg and ketorolac, 0.4 mg/kg on platelet function in ten volunteers using a double-blind, randomized crossover design. Coagulation was evaluated using the following tests: PT, APTT, factor V and VII and bleeding time. Platelet aggregation after administration of adrenalin and ADP was measured, these tests were done at 2 and
24 hours after medication administration. Propacetamol and ketorolac both decreased thromboxane concentration at 2 hours after administration. Ketorolac alone decreased ADP induced platelet aggregation at 2 and 24 hours following the one IV dose. Although ketorolac did prolong bleeding time slightly, coagulation was statistically unaffected.

Ketorolac suppresses postoperative bladder spasms after pediatric ureteral reimplantation

Park JM, Houck CS, Sethna NF et al. Anesth Analg 2000; 91: 11-15

This randomized, double-blinded study evaluated the efficacy of ketorolac in suppressing postop bladder spasm in children who had undergone ureteral reimplantation. All patients had epidural bupivacaine 0.1% and fentanyl 2 mcg/ml for post op analgesia and were given either placebo or ketorolac 0.5 mg/kg IV every 6 hours for 48 hours. 25% (4/12) of the ketorolac group and 83% (10/12) of the control group experienced bladder spasms. The severity of the spasms was greater in the control group (2.6) compared to the ketorolac group (1.2) using a 3-point scale to score severity. No bleeding complications were noted.

The effect of postoperative non-steroidal anti-inflammatory drug administration on spinal fusion.

Glassman SD, Rose MS, Dimar JR et al. Spine 1998; 7:834-838

This paper describes a retrospective review of 288 patients who underwent an instrumented spinal fusion. The report includes 288 patients whose surgeries were between the years of 1991-1993, 121 of whom received no non-steroidal medications and 167 of whom received ketorolac. The groups were similar with regard to demographics.

Ketorolac significantly affected the rate of nonunion. There were 29 non-unions reported in the group who received ketorolac and 5 non-unions in the group who received no non-steroidal medications. This difference is significant to the P< 0.001 level. Since nonunion was diagnosed only at reexploration, by hardware failure of with tomgrams the incidence of nonunion was likely underreported.

The mean number of ketorolac doses which the nonunion group received was 26, while the mean number of doses of ketorolac in the patients who did not develop nonunion was 12. The dose of ketorolac used was a 60 mg IM loading dose followed by 30 mg every 6-8 hours PRN pain. Some of the patients received additional 10 mg PO ketorolac after parenteral treatment had completed.

Recombinant human bone morphogenic protein-2 overcomes the inhibitory effect of ketorolac on posterolateral lumbar intertransverse process spine fusion.

Martin GJ, Boden SD, Titus L. Spine 1999; 24: 2188-2194

There were three groups in this study using an established rabbit model. All animals underwent single-level lumbar fusion with autologous bone graft following which mini-osmotic pumps were implanted subcutaneously. Group one received saline via the pump, group 2 ketorolac at a dose of 4 mg/kg/day and group 3 received ketorolac and also the bone morphogenic protein mentioned in the title. This protein has been proven to enhance fusion rate according to the authors. 75% of the control group, 35% of the ketorolac group and 100% of group 3 (ketorolac + the morphogenic protein) were judged to have solidly fused vertebrae. Radiographs and histology were used to determine the presence of a stable fusion. The difference between group 1 and 2 was significant to a P = 0.037. In the discussion, the authors' state that the dose of ketorolac administered via the subcutaneous infusion pump, 4 mg/kg/day, is equivalent to the adult does of 1-2 mg/kg/day.

Minimizing the adverse effects of ketorolac.

Reinhart D. Drug Safety 2000; 22: 487-497

The author of this review article with 74 references is an anesthesiologist.

Commentary by Thomas J Mancuso, MD, FAAP:

I think that several conclusions can be drawn from this group of papers. Certainly ketorolac is an effective postoperative analgesic for a variety of procedures. Carney's paper in the journal of pediatric surgery demonstrates it's effectiveness in a variety of post-op patients using a dose of 0.5 mg/kg IV Q6H and the study by Lieh-Lai in Critical Care Medicine shows the approximate equivalence of one dose of 0.6 mg/kg IV ketorolac to 0.1 mg/kg IV morphine in the postoperative setting, again after a variety of procedures.

What about complications as a result of the use of ketorolac? In Lieh-Lai's paper, 15 patients received one dose ketorolac following spinal fusion with no reported deleterious effects. The two papers from Spine do support the argument that the drug may inhibit bone fusion. Although the paper by Glassman is a retrospective review and some patients with nonunion may have received many more doses than would currently be given, since nonunion is such a serious complication of spinal fusion and instrumentation, it seems prudent to avoid ketorolac in these patients. The laboratory investigation by Martin also demonstrates an effect on bone fusion in a rabbit model, but I am uncertain of the equivalence of SQ infusion of 4 mg/kg/day in a rabbit and IV administration of 2 mg/kg/day in a human. The paper is followed by comments by Dr. Einhorn, the Chairman of Orthopaedics at Boston University Medical School. He comments that inhibitory effects on long bone fracture healing have not yet been demonstrated and wonders whether the inhibitory effect on spinal fusion is more pronounced in lower animals and of no clinical significance in humans.

The role ketorolac plays in postoperative bleeding is also uncertain. Niemi, in Acta Anaesthesiologica Scandinavica, demonstrates abnormal platelet function up to 24 hours following a single dose of ketorolac. 0.4 mg/kg IV in a randomized crossover study using healthy volunteers. He also noted that coagulation, measured with PT, APTT, factor V and VII was not affected. In Lieh-Lai's paper from Critical Care Medicine, abnormal postoperative bleeding was not seen after one dose of 0.6 mg.kg IV and her study included children who had undergone spine fusions, cardiac and neurosurgical procedures. Park's paper in Anesthesia and Analgesia demonstrates the effectiveness of 0.5 mg/kg IV Q6H ketorolac in suppressing bladder spasms with not noticeable difference in hematuria or any reported bleeding complications. Carney used the same dose and schedule following a variety of general surgical procedures with no identified alteration in bleeding complications.

As these papers show, we have incomplete data. I certainly do not want to be responsible for a postoperative complication such as hemorrhage or nonunion of a spinal fusion. On the other hand, I have cared for PSF patients who were suffering many opioid-related side effects with only adequate analgesia. These adolescents were lying in bed, tired, defeated-looking, hypoventilating, cooperating very poorly, if at all, with incentive spirometry, suffering with nausea making and still complaining of discomfort. The addition of a short (24hour) course of ketorolac in this sort of situation might prevent serious pulmonary complications, speed recovery and allow oral intake to begin. I feel more certain that ketorolac's benefits outweigh it's disadvantages in postoperative general surgical patients based on papers such as Park's and Carney's but I do not administer the drug without discussion with my colleague on the other side of the ether screen who will be held accountable for post operative complications should the occur.

Pediatric spinal injuries.

Reynolds, R Current Opinion in Pediatrics 2000;12:67-71

This paper is a review of the topic from the perspective of a pediatrician. Mechanisms of injury include falls from height (compression injuries) sports and in the more severe injuries, motor vehicle accidents. Development and ossification of the cervical spine is briefly reviewed and the various level of fracture discussed. Evaluation, including radiographic examinations as well as management are reviewed.

Characteristics of pediatric cervical spine injuries.

Kokoska ER, Keller MS, Rallo MC Journal of Pediatric Surgery 2001; 36: 100-105

The authors reviewed the National Pediatric Trauma Registry between the dates April 1994 and March 1999 and identified all cases with blunt trauma with cervical fractures, dislocations and spinal cord injuries without radiographic abnormality (SCIWORA). The authors found an incidence of 1.6%. the most common causes of the cervical spine injuries were auto accidents and sports. in this review, younger children more commonly had upper spine injuries. Most children with fractures (83%) and none of the children with dislocations only had no neurologic sequelae. Mortality was generally associated with concomitant brain injuries, not isolated cervical spine injury.

cervical spine injuries: defining the disease

Patel JC, Tepas JJ, Mollit DL et al Journal of Pediatric Surgery 2001; 36: 373-376

The authors reviewed all children entered into the National Pediatric Trauma Registry over a consecutive 10-year period. From a total of over 75,000 entries, 1,098 children with cervical spine injury were identified, an incidence of 1.5% in the group of children entered into the registry. Motor vehicle accidents were the most common mechanism of injury. In cases where the child was an occupant, not a pedestrian,
61% of the children were unrestrained. One third of the children had neurologic injury and one-half of these do not have any radiographic evidence of bony injury. In contrast, 50% of children with spinal cord injury had no radiologic abnormality. Upper spine injury was distributed equally among various age groups, while lower cervical spine injury was more common in the older ( > 8 years of age) children. Mortality was highest among those with upper spine injury, particularly those with atlanto-occipital dislocation. The authors do not endorse any particular radiographic exam in the evaluation of a pediatric trauma victim in view of the high incidence of non-diagnostic examinations among children with either cervical spine or spinal cord injury.

Commentary by Thomas J Mancuso, MD, FAAP

The 10-year review of the National Pediatric Trauma Registry for cervical spine injury was published the month following the publication of the five year review of the same database for virtually the same topic. Fortunately, the two papers agree substantially. Cervical spine injury in children is relatively rare and often results from motor vehicular trauma. Complete spinal cord injury in uncommon, mortality in unfortunately high in children who do suffer cervical spine and/or spinal cord injury and highest in those who suffer atlanto-occipital dislocation. Both papers comment that pediatric trauma victim with a significant injury should be assumed to have an unstable neck until definitively proven otherwise.

The paper by Patel, which reviewed 10 years of experience, did not find that upper cervical spine injuries were limited to younger children, but were equally prevalent in all age groups. Kokoska described the syndrome of spinal cord injury without radiographic abnormality (SCIWORA), a condition almost unheard of in adults but which he states occurs in 15-25% of pediatric cervical spine injuries.

These papers certainly document nicely the demographic of pediatric cervical spine injury and unfortunately we are left with the same uncertainly we had previously. In children with significant injuries at risk for this condition, radiologic examination cannot completely rule out cervical spine injury and we must consider this uncertainty in planning any airway interventions.

Current approach to pediatric syncope.

Jonsrude CL. Pediatric Cardiology 2000; 21: 522-531

Syncope is defined here as abrupt loss of consciousness that reverses without intervention. This can occur when cerebral blood flow decreases to < 30%-50% of normal. The author focuses this paper on issues of concern to a pediatric cardiologist to whom a child is referred for evaluation of syncope and therefore limits his remarks to cardiac causes. The paper does include a able of various causes for syncope in children according to system. Neurologic causes include: seizures, migraine headache, TIA and acute vestibular syndrome. Psychiatric causes include; depression, conversion reaction or panic attacks. Systemic causes include; Co effect, drugs of abuse or abnormal electrolyte. He states that 15%-25% of children and adolescents experience at least one episode of syncope by the time they reach adulthood. The evaluation of syncope can be very extensive and expensive, encompassing blood tests, radiographic studies of the chest and head, ECG and even holter monitoring despite the fact that very often the underlying cause is not a serious medical problem.

Neurally-mediated syncope (NMS) is the most common of the cardiac causes for syncope. Reflex syncope, a variant of NMS, results from an exaggerated respiratory sinus arrthymia followed by hypotension upon assuming an upright posture. In postural orthostaic hypotension syndrome (POTS) which is another variant of NMS, patients exhibit exaggerated sinus tachycardia upon standing followed by systemic hypotension. NMS peaks in incidence between 15-19 years of age. NMS patients typically can indentify three stages; a prodrome consisting of lightheadedness, dizziness and perhaps nausea which may last for seconds or minutes, loss of consciousness, and recovery. A subset of NMS patients exhibit posturing, gross tonic-clonic movements. The movements are associated with profound hypotension and asystole, but with simultaneous slow waves on EEG which is evidence of decreased cerebral blood flow, not epileptiform activity.

The evaluation of children referred to a cardiologist for syncope can be extensive, including head upright tilt table testing (HUTT), ambulatory ECG,
echocardiography and exercise stress testing. Although the cornerstone of treatment for children with NMS is education and reassurance, the article has a complete table of the various medication used in the treatment of this condition. The list includes: fludrocortisone, midrodine, methylphenidate, beta-blockers, SSRI's, and others.

Commentary by Thomas J Mancuso, MD, FAAP

If your preop questionaire includes inquiries about syncope, 15%-25% of respondents will answer in the affirmative and many of them will already have seen a cardiologist and perhaps even be taking one of the medications listed in this paper. In addition, the review of normal hemodynamic mechanisms in posture changes as well as the explanation of the abnormal physiology involved in children with NMS is of interest. #include ./footer_include.iphtml