Stable plasma concentrations of unbound ropivacaine during postoperative epidural infusion for 24-72 hours in children.

BACKGROUND AND OBJECTIVES: The aim of this open, non-controlled, multi-centre study was to evaluate the pharmacokinetics and safety of a 24-72 h continuous epidural ropivacaine infusion in children aged 1-9 yr. METHODS: After induction of general anaesthesia, 29 ASA I-II children, scheduled for major surgery in dermatomes below T10 had lumbar epidural catheters placed. A bolus of ropivacaine, 2 mg kg(-1), was given over 4 min, followed immediately by an infusion of 2 mg mL(-1) ropivacaine 0.4 mg kg(-1) h(-1) for the next 24-72 h. RESULTS: Plasma concentrations of total ropivacaine (mean 0.83 and 1.06 mg L(-1) at 16-31 and 59-72 h, respectively) and alpha1-acid-glucoprotein (mean 13 and 25 micromol L(-1) at baseline and 59-72 h) increased over the course of the infusion. Plasma concentrations of unbound ropivacaine were stable throughout the epidural infusion (mean 0.021 range 0.011-0.068 and mean 0.016 range 0.009-0.023 mg L(-1) at 16-31 and 59-72 h, respectively) and were well below threshold levels associated with central nervous system toxicity in adults (0.35 mg L(-1)). Apparent unbound clearance (mean 346, range 86-555 mL min(-1) kg(-1)) showed no age-dependency. No signs of systemic toxicity or cardiovascular effects were observed. All patients received additional analgesics with morphine. CONCLUSION: Following a 24-72 h epidural infusion of ropivacaine 0.4 mg kg(-1) h(-1) in 1-9-yr-old children, the plasma concentrations of unbound ropivacaine were stable over time with no age-dependency.

Craniocerebral magnetic resonance imaging measurement and findings in Lesch-Nyhan syndrome.

OBJECTIVE: To provide the first comprehensive magnetic resonance imaging (MRI) assessment of brain in a series of patients with Lesch-Nyhan syndrome (LNS), with emphasis on basal ganglia measurements. DESIGN: Routine readings of MRI studies, repeated reading in random order blinded to subject diagnosis, and 3-dimensional volumetric measures of basal ganglia regions. SETTING: The Johns Hopkins Hospital, Baltimore, Md. PATIENTS: Seven patients with LNS who have hypoxanthine guanine phosphoribosyltransferase levels less than 1.6% and characteristic clinical features of the disorder, which include hyperuricemia, cognitive impairment, and dystonic movement disorder, were compared with 7 age-matched control subjects. Five of the 7 patients demonstrated self-injurious behavior. MRI studies were performed using general anesthesia because of the severity of the movement disorder. MAIN OUTCOME MEASURES: Measurement of brain regions from MRI-obtained images. RESULTS: Routine readings described mild cerebral atrophy in 2 of 7 patients, but no caudate or putamen abnormalities were reported. However, on the directed blinded rereading, small caudates were suspected in 5 of 7 cases, and abnormalities in cerebral size and cranium were identified. Volumetric studies of the patients with LNS confirmed a 34% decrease in caudate volume (P<.001), a 17% decrease in total cerebral volume (P<.03), and a 12% decrease in putamen volume (P=.19). CONCLUSIONS: To our knowledge, this is the first demonstration of consistent neuroanatomic abnormalities in LNS. The findings of reduced basal ganglia volume are consistent with the dystonic movement disorder.

Knockdown of spinal cord postsynaptic density protein-95 prevents the development of morphine tolerance in rats.

The activation of spinal cord N-methyl-D-aspartate (NMDA) receptors and subsequent intracellular cascades play a pivotal role in the development of opioid tolerance. Postsynaptic density protein-95 (PSD-95), a molecular scaffolding protein, assembles a specific set of signaling proteins around NMDA receptors at neuronal synapses. The current study investigated the possible involvement of PSD-95 in the development of opioid tolerance. Opioid tolerance was induced by intrathecal injection of morphine sulfate (20 microg/10 microl) twice a day for 4 consecutive days. Co-administration of morphine twice daily and PSD-95 antisense oligodeoxynucleotide (50 microg/10 microl) once daily for 4 days not only markedly reduced the PSD-95 expression and its binding to NMDA receptors in spinal cord but also significantly prevented the development of morphine tolerance. In contrast, co-administration of morphine twice daily and PSD-95 missense oligodeoxynucleotide (50 microg/10 microl) once daily for 4 days did not produce these effects. The PSD-95 antisense oligodeoxynucleotide at the doses we used did not affect baseline response to noxious thermal stimulation or locomotor function. The present study indicates that the deficiency of spinal cord PSD-95 attenuates the development of opioid tolerance. These results suggest that PSD-95 might be involved in the central mechanisms of opioid tolerance and provide a possible new target for prevention of development of opioid tolerance.

Evidence of neuronal excitatory amino acid carrier 1 expression in rat dorsal root ganglion neurons and their central terminals.

The expression and distribution of the neuronal glutamate transporter, excitatory amino acid carrier-1 (EAAC1), are demonstrated in the dorsal root ganglion neurons and their central terminals. Reverse transcriptase-polymerase chain reaction shows expression of EAAC1 mRNA in the dorsal root ganglion. Immunoblotting analysis further confirms existence of EAAC1 protein in this region. Immunocytochemistry reveals that approximately 46.6% of the dorsal root ganglion neurons are EAAC1-positive. Most EAAC1-positive neurons are small and around 250-750 microm2 in surface area, and some co-label with calcitonin gene-related peptide (CGRP) or isolectin IB4. In the spinal cord, EAAC-1 immunoreactive small dot- or patch-like structures are mainly localized in the superficial dorsal horn, and some are positive for CGRP or labeled by isolectin IB4. Unilateral dorsal rhizotomy experiments further show that EAAC1 immunoreactivity is less intense in superficial dorsal horn on the side ipsilateral to the dorsal rhizotomy than on the contralateral side. The results indicate the presence of EAAC1 in the dorsal root ganglion neurons and their central terminals. Our findings suggest that EAAC1 might play an important role in transmission and modulation of nociceptive information via the regulation of pre-synaptically released glutamate.

Epidural analgesia in the management of severe vaso-occlusive sickle cell crisis.

OBJECTIVES: To determine whether continuous epidural analgesia could effectively decrease pain and thereby improve the management of severe vaso-occlusive crisis in children with sickle cell disease who were unresponsive to conventional analgesic therapy. DESIGN: Retrospective observational study. SETTING: A tertiary care hospital with a large pediatric sickle cell patient referral population. PATIENTS: The study describes nine children in 11 painful vaso-occlusive crises, unresponsive to high-dose systemic opioids, nonsteroidal anti-inflammatory drugs, and adjunctive measures, who underwent continuous epidural analgesia to control pain. OUTCOME MEASURES: Subjective pain scores, arterial oxygen saturation monitoring, and plasma lidocaine levels. METHODS: Placement of an epidural catheter for the administration of a continuous infusion of local anesthetic, alone, or in combination with fentanyl, in the management of vaso-occlusive crisis. RESULTS: An initiation of epidural analgesic therapy, 8 of 9 patients reported severe pain (8 to 10 on a scale of 0 to 10, 0 = no pain, 10 = the worst pain they ever experienced). Analgesic was immediate (pain score 0 to 2) in 8 of 9 patients, and continuously effective in 9 of 11 crises. Five patients required either the addition of fentanyl or changing the local anesthetic from lidocaine to bupivacaine to maintain analgesia for 2 to 5 days. In 7 of 9 patients, oxygen saturation dramatically increased from 87 to 95% to 99 to 100% after epidural analgesia was initiated. In all patients, plasma lidocaine levels ranged from 1.1 to 4.6 mg/L and dose-related toxicity did not occur. One patient developed hypotension secondary to high sympathetic blockade (T-4), one had an inadvertent dural puncture during insertion of the catheter, one had the epidural catheter removed for fever, and one achieved analgesia only transiently. There were no other complications, and epidural analgesia was not associated with sedation, respiratory depression, or limitation of movement. All epidural catheters were cultured on removal, and colonization did not occur. CONCLUSIONS: Epidural analgesia with local anesthetics administered alone or in combination with fentanyl effectively and safely treats the pain of sickle cell vaso-occlusive crisis unresponsive to conventional pain management and does so without causing sedation, respiratory depression, or significant limitation on ambulation. Furthermore, early treatment of painful crisis with this technique may improve oxygenation, a critical factor in the evolution of further sickling.

Penile nerve block for newborn circumcision.

Circumcision in neonates is performed, almost universally, without anesthesia or analgesia. It is associated with pain, crying, agitation, and physiologic stress. Twenty infants receiving penile nerve block for circumcision were compared with ten infants having circumcision without anesthesia. Heart rate and blood pressure rose 34 and 15%, respectively, in unblocked infants, and were unchanged in infants receiving local anesthesia. Oxygen saturation declined 16% in unanesthetized infants compared with 6% in blocked infants (P less than .03). Anesthetized infants were less agitated and cried less. Peak plasma concentrations of the local anesthetic lidocaine averaged 0.51 +/- 0.17 microgram/mL (range 0.1-1.6), well below accepted toxic levels. There were no local or systemic complications.

Pain and symptom control in terminally ill children.

The management of pain in terminally ill pediatric patients has incalculable benefits to patients, their families, and physicians and nurses. A therapeutic management plan is dependent on a thorough understanding of the causes of pain in these patients, on pain assessment, and on the myriad drugs and drug strategies that are essential in pain treatment. Aggressive symptom control of treatment-related side effects can ensure successful implementation of such a plan.

The management of pain in sickle cell disease.

The pain of vaso-occlusive crisis in patients with sickle cell disease is excruciating, incapacitating, and sometimes refractory to even the most advanced analgesic treatments. A comprehensive, multimodal approach to therapy that includes education, cognitive therapies, anti-inflammatory drugs, opioids, and psychostimulant adjuvant drugs has been presented. Until a cure for the underlying disease is found, these are the best approaches available. The authors hope that future research will find even better modalities of analgesic care.

The night after surgery. Postoperative management of the pediatric outpatient--surgical and anesthetic aspects.

Outpatient or "ambulatory" anesthesia and surgery has revolutionized the way surgery is practiced in the United States. Safe, reliable, inexpensive, and convenient outpatient surgery is an attractive option for parents, children, health care providers, and insurers.

Pediatric acute pain management.

The past decade has brought about an explosion of knowledge about the physiology of nociception and many new techniques for pain relief, new analgesic drugs, and new applications of old analgesic drugs. These techniques include methods of opioid administration by transdermal and transmucosal absorption and the use of neuraxial analgesia for the management of pain in children. Interest in the use of regional anesthesia in children has been rekindled, and analgesic properties and pre-emptive analgesic properties of many agents not typically considered analgesics, such as clonidine and ketamine, have been recognized. Perhaps the greatest advance has been the paradigm shift in the recognition that pain not only exists in infants and children but also is a significant cause of morbidity and even mortality. Given the unprecedented interest in pain management in adults and children, physicians can now look forward to the development of new methods of drug delivery and of receptor-specific drugs that divorce analgesia from the untoward side effects of existing analgesics. Improvement in the quality of life of hospitalized children also will occur.

Life-threatening airway obstruction as a complication to the management of mediastinal masses in children.

Life-threatening airway obstruction from large mediastinal masses in children poses a difficult diagnostic and therapeutic dilemma, requiring the close coordination of a pediatric surgeon, anesthesiologist, radiologist, and oncologist. To focus on this problem, the anesthetic and surgical management of 50 consecutive children with mediastinal masses treated between 1978 and 1984 were reviewed. Thirty children presented with respiratory symptoms; nine had life-threatening respiratory compromise with dyspnea, orthopnea, and stridor. Thirteen of these symptomatic children had marked compression of the trachea and/or mainstem bronchi on radiographic studies. The tracheal cross-sectional area which was measured by computed tomography was decreased by 35% to 93% of the normal tracheal dimensions in these children. Nonresectable malignant neoplasms including lymphoma, Hodgkin's disease, rhabdomyosarcoma, and neuroblastoma were the eventual diagnoses in 10 of these patients. The other 3 patients were less than 4 years old and had benign lesions. General anesthesia was judged to be prohibitively risky in 5 of 13 patients. The diagnosis was established by node or needle biopsy under local anesthesia, and general anesthesia was deferred until the compromised airway was alleviated by radiation and chemotherapy. General anesthesia with endotracheal intubation was administered to 8 patients, 5 of whom developed total airway obstruction. Using a variety of maneuvers, ventilation was reestablished in all 5 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of successful primary closure of congenital abdominal wall defects using intraoperative measurements.

To determine whether intragastric pressure (IGP) and central venous pressure (CVP) would reliably predict successful primary closure of congenital abdominal wall defects (omphalocele/gastroschisis) in newborn infants, we developed the following prospective intraoperative management protocol. Following a temporary trial of fascial closure, infants who had an IGP less than 20 mm Hg or an increase in CVP of less than 4 mm Hg were primarily closed. If IGP was greater than 20 mm Hg or if CVP increased by more than 4 mm Hg, the temporary closure of the abdomen was reopened and a prosthetic silo was placed. Ten infants who were less than 24 hours old and averaged 2.7 kg (range, 1.4 to 4.2 kg) and 37-weeks gestation (range, 32 to 41 weeks) were studied. Eight infants met criteria for primary closure. Their IGP averaged 14 +/- 4 mm Hg (+/- SD) (range, 8 to 19 mm Hg), and their increase in CVP averaged 1 +/- 2 mm Hg (range, -2 to 3 mm Hg). In the two infants who required staged repair, IGP averaged 25 +/- 1 mm Hg (+/- SD) (range, 24 to 25 mm Hg), and the increase in CVP averaged 7 +/- 1 mm Hg (range, 6 to 8 mm Hg). All patients were anesthetized with fentanyl (12.5 micrograms/kg) and paralyzed with metocurine (0.3 mg/kg) intraoperatively. There were no postoperative complications in either group of patients related to increased intraabdominal pressure, and all patients were extubated within 48 hours of the initial surgery. We conclude that the intraoperative measurement of changes in IGP and CVP can serve as a guide to the operative management of congenital abdominal wall defects and can reliably predict successful outcome following repair.

Pain management in the critically ill child.

Children frequently received no treatment, or inadequate treatment, for pain and for painful procedures. The newborn and critically ill children are especially vulnerable to no treatment or under-treatment. Nerve pathways essential for the transmission and perception of pain are present and functioning by 24 weeks of gestation. The failure to provide analgesia for pain results in rewiring the nerve pathways responsible for pain transmission in the dorsal horn of the spinal cord and results in increased pain perception for future painful results. Many children would withdraw or deny their pain in an attempt to avoid yet another terrifying and painful experiences, such as the intramuscular injections. Societal fears of opioid addiction and lack of advocacy are also causal factors in the under-treatment of pediatric pain. False beliefs about addictions and proper use of acetaminophen and other analgesics resulted in the failure to provide analgesia to children. All children even the newborn and critically ill require analgesia for pain and painful procedures. Unbelieved pain interferes with sleep, leads to fatigue and a sense of helplessness, and may result in increased morbidity or mortality.

The pharmacologic management of pain in children.

We have attempted to dispel many of the myths and misconceptions surrounding the use of narcotic analgesics in the treatment of childhood pain. Our hope is that an improved understanding and application of effective and safe therapies will minimize the suffering of the child with acute or chronic pain.