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.     

Intrathecal morphine for pediatric renal transplant recipients

Many pediatric renal transplant recipients have significant discomfort in the early postoperative period despite opioid administration. Intrathecal morphine is safe and effective for pain control in children. We examined our results with the use of intrathecal morphine for postoperative analgesia in renal transplant recipients at our institution. The morphine was administered while the patients were under general anesthesia. Seventeen of 22 patients received excellent pain control and there were few minor and no major complications. Intrathecal morphine is beneficial for postoperative analgesia in pediatric renal transplant recipients.     

Peripheral opioids in inflammatory pain

Topically applied opioids have provided effective analgesia without adverse effects, including tolerance, in adult patients with painful inflammatory conditions. The presumed mechanism of action is by interaction with opioid receptors which are sited on sensory nerve terminals and which may be up-regulated in inflammation. The use of peripherally acting opioids has not been studied in paediatric patients. The use of topical morphine gel is reported in two children with epidermolysis bullosa, where acute inflammatory pain is a major symptom and where effective analgesia is a major clinical problem. The gel provided rapid reduction in pain scores in the patients and without any reported adverse effects or tolerance. A topical route of analgesia might be extremely beneficial for children with other painful skin lesions, including burns or post-surgical wounds, and further studies are now required.     

Peripheral opioids in inflammatory pain.

Topically applied opioids have provided effective analgesia without adverse effects, including tolerance, in adult patients with painful inflammatory conditions. The presumed mechanism of action is by interaction with opioid receptors which are sited on sensory nerve terminals and which may be up-regulated in inflammation. The use of peripherally acting opioids has not been studied in paediatric patients. The use of topical morphine gel is reported in two children with epidermolysis bullosa, where acute inflammatory pain is a major symptom and where effective analgesia is a major clinical problem. The gel provided rapid reduction in pain scores in the patients and without any reported adverse effects or tolerance. A topical route of analgesia might be extremely beneficial for children with other painful skin lesions, including burns or post-surgical wounds, and further studies are now required.     

Pharmacologic management of pain in children and adolescents

In the management of chronic pain conditions, the combination of pharmacologic measures with physical and psychologic modalities becomes even more important. A pain clinic and pain consultation service are one model that facilitates this combined approach. Initial management of mild to moderate pain begins with nonopioid analgesics such as acetaminophen and NSAIDs. Persistent severe pain of a neuropathic character merits careful trials of antidepressants or anticonvulsants. Traditionally, use of opioids for chronic pain not due to cancer has been discouraged for adults as well as children. Recently, this view was challenged by reports by Portenoy and Foley and by Taub, who followed a group of adults with chronic pain due to a variety of conditions. They found that the majority of these patients, if managed with opioids on a regular schedule as part of an overall treatment program, could be made comfortable and were able to increase their level of functioning for several years. In general, dosage escalation and compulsive drug-seeking behaviors were not seen. Since this report was retrospective and did not involve children, caution must be applied in extrapolating these findings to children. For example, remarkably little is known about the effects of chronic opioid administration in childhood on growth and development. Certainly, this issue deserves further study before general recommendations can be made. It seems prudent to emphasize the importance of maximizing nonpharmacologic and nonopioid approaches in the management of chronic pain in children prior to embarking on long-term use of opioids.     

Postoperative Schmerztherapie bei Kindern

Undertreatment of postoperative pain in children remains a problem. Reasons include lack of pain assessment, lack of knowledge about age-related physiological and pharmacological aspects, and fear of the side effects of opioids. When children need analgesics, it is important to choose a comfortable administration route of (no intramuscular injections!). Nonopioid analgesics such as acetaminophen are used after minor surgical procedures. The use of opioids requires individual dose titration and careful monitoring of side effects; they can be administered intravenously either as a continuous infusion or via a patient-controlled system. Nerve blocks applied intraoperatively provide good pain relief, and another option is epidural analgesia with local anesthetics and/or opioids. Adjuvant analgesics and nonpharmacologic interventions such as transcutaneous electrical nerve stimulation are used according to the underlying pain pathophysiology, primarily in patients suffering from neuropathic pain. The establishment of pain services and comprehensive education of both nursing and medical staff can help improve postoperative pain therapy in children.     

Parenteral Acetylsalicylic Acid Treatment in Children with Sickle Cell Pain Crisis: A Preliminary Report

Bone vasocclusive crisis (VOC) is a frequent reason for hospitalization of children with sickle cell disease. In spite of significant efforts, no effective antisickling agent has been found, and hydration and analgesia are the recommended modes of treatment.Oral aspirin, acetaminophen, or codeine is recommended for mild pain, as is a parenteral narcotic for moderate or severe crises.     

Nimesulide, a cyclooxygenase-2 preferential inhibitor, impairs renal function in the newborn rabbit

Tocolysis with nonsteroidal anti-inflammatory drugs (NSAIDs) has been widely accepted for several years. Recently, the use of the cyclooxygenase-2 (COX2) preferential NSAID nimesulide has been proposed. However, data reporting neonatal acute renal failure or irreversible end-stage renal failure after maternal ingestion of nimesulide question the safety of this drug for the fetus and the neonate. Therefore, this study was designed to define the renal effects of nimesulide in newborn rabbits. Experiments were performed in 28 newborn rabbits. Renal function and hemodynamic parameters were measured using inulin and para-aminohippuric acid clearances as markers of GFR and renal blood flow, respectively. After a control period, nimesulide 2, 20, or 200 microg/kg was given as an i.v. bolus, followed by a 0.05, 0.5, or 5 microg.kg(-1).min(-1) infusion. Nimesulide administration induced a significant dose-dependent increase in renal vascular resistance (29, 37, and 92%, respectively), with a concomitant decrease in diuresis (-5, -23, and -44%), GFR (-12, -23, and -47%), and renal blood flow (-23, -23, and -48%). These results are in contrast with recent reports claiming that selective COX2 inhibition could be safer for the kidney than nonselective NSAIDs. These experiments confirm that prostaglandins, by maintaining renal vasodilation, play a key role in the delicate balance regulating neonatal GFR. We conclude that COX2-selective/preferential inhibitors thus should be prescribed with the same caution as nonselective NSAIDs during pregnancy and in the neonatal period.     

Acetaminophen toxicity in children

Acetaminophen is widely used in children, because its safety and efficacy are well established. Although the risk of developing toxic reactions to acetaminophen appears to be lower in children than in adults, such reactions occur in pediatric patients from intentional overdoses. Less frequently, acetaminophen toxicity is attributable to unintended inappropriate dosing or the failure to recognize children at increased risk in whom standard acetaminophen doses have been administered. Because the symptoms of acetaminophen intoxication are nonspecific, the diagnosis and treatment of acetaminophen intoxication are more likely to be delayed in unintentional cases of toxicity. This statement describes situations and conditions that may contribute to acetaminophen toxicity not associated with suicidal intentions.     

Ibuprofen in childhood: evidence-based review of efficacy and safety]

Ibuprofen is the non-steroidal anti-inflammatory drug most prescribed for the treatment of fever and moderate pain in childhood. Its analgesic and antipyretic efficacy is now well documented: at equal doses ibuprofen appears slightly more effective than acetaminophen in the treatment of fever and is equivalent for analgesia. However, adverse effects should be taken into account in the choice between ibuprofen and acetaminophen. Lot of studies (case reports, cohort studies, case-control studies and one multicenter double-blind randomized control trial) have reported ibuprofen adverse effects at therapeutics doses. These data suggest there is an increased risk of invasive group A streptococcal infection after chickenpox and of acute renal failure in case of hypovolemia after a treatment by ibuprofen. Gastroduodenal and hemorrhagic adverse events could also happen, but the causality with ibuprofen is not demonstrated. Therefore, ibuprofen is not recommended for the treatment of fever or moderate pain during chickenpox or during a disease with a risk of dehydration, until other pharmacoepidemiology studies more accurately quantify the risk of adverse events of ibuprofen in children.     

A comparative analysis of the use of mycophenolate mofetil in pediatric vs. adult renal allograft recipients

Mycophenolate mofetil (MMF) is a new immunosuppressive drug used in combination with cyclosporin A (CsA) or tacrolimus and prednisone to prevent rejection of renal allografts in both adult and pediatric recipients. It has been shown in several large studies that MMF significantly decreases the incidence of acute rejection in adults and has acceptable adverse effects. In this retrospective study, we compare the incidence of adverse events between pediatric and adult renal allograft recipients. Twenty-two children and 37 adult renal allograft recipients were included in the study. The initial dose of MMF was 1.5 g b.i.d. for the adult patients and ranged from 15 to 30 mg/kg/d for the pediatric patients. All patients received p.o. acyclovir as prophylaxis for cytomegalovirus (CMV). The two groups were similar regarding gender distribution and graft source. Acute rejections occurred in 10 of the 22 pediatric patients (45%) and in nine of the 37 adults (24%), p = NS. The incidence of infections was similar in both groups except for the occurrence of CMV (n = 5), which was seen only in adults. The incidence of GI symptoms was significantly higher in the pediatric population (54.5% vs. 21.6%; p = 0.02). Significant weight loss was seen more often in the smaller pediatric patients (weight < or = 15 kg) compared to the larger pediatric patients, 60% vs. 11.7%, p = 0.05. Among the patients who had significant GI symptoms 50% of the adults and 75% of the pediatric recipients required either dose reduction or, most commonly, discontinuation of the MMF. The need to discontinue MMF was significantly higher in the pediatric patients, especially in those that weighed less than 15 kg. We suggest the possibility that the optimum dose, dosing interval or preparation of MMF has not yet been established for pediatric patients. One should therefore monitor pediatric patients closely, especially the small ones, to avoid significant nutritional problems and other adverse GI events.     

Chronic acetaminophen overdosing in children: risk assessment and management

Acetaminophen is currently the pediatric analgesic and antipyretic of choice. Although children appear to tolerate single, high-dose ingestions well, the literature is replete with reports of significant morbidity and mortality after repeated supra-therapeutic dosing. Proposed risk factors for injury with chronic use include age, total dose, duration, presence of intercurrent febrile illness, starvation, co-administration of cytochrome P450-inducing drugs, underlying hepatic disease, and unique genetic makeup. Evaluation of these children should include serum acetaminophen concentration, prothrombin time, and serum bilirubin and transaminase concentrations. The Rumack-Mathew nomogram should not be used to estimate the risk of hepatotoxicity in cases of chronic ingestion. Based on history, clinical examination, and laboratory findings, patients may be placed in three categories: those without hepatic injury and with no residual acetaminophen to be metabolized, those without injury but with some acetaminophen to be metabolized, and those with hepatotoxicity. Those without injury and no residual acetaminophen need not be treated or followed. Patients with hepatotoxicity or potential for hepatotoxicity based on residual acetaminophen should be treated with N-acetylcysteine. Most importantly, because so many parents are unaware of the potential risk of inappropriate dosing, education is the key to preventing future cases.     

The adverse renal effects of prostaglandin-synthesis inhibition in the fetus and the newborn

OBJECTIVES:

To summarize experimental animal data and to provide a limited literature review on the adverse renal effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the developing fetus and the maturing newborn.

DATA:

The experimental data were obtained from anesthetized, ventilated, six- to eight-day-old rabbits that received an intravenous bolus of either acetylsalicylic acid (ASA), ibuprofen (IBU) or indomethacin (INDO). In one set of experiments, ASA was also tested in 12-week-old (young adult) rabbits. Renal function was monitored with inulin and para-aminohippuric acid clearances measuring glomerular filtration rate (GFR) and renal blood flow. The renal vascular resistance was calculated. All three nonspecific cyclo-oxygenase-1 or -2 (COX-1/2) inhibitors caused remarkably similar reversible, oliguric, acute renal failure (ARF). In young adult animals, the side effects were attenuated. The underlying pathophysiology is related to the carefully maintained low GFR of the fetus and the newborn, dependent on a delicate interplay between vasoconstriction (angiotensin II) and vasodilation (prostaglandins [PGs]). When PG-synthesis is inhibited, the vasoconstriction is relatively unopposed, causing ARF.

LITERATURE REVIEW:

The renal effects of fetal exposure to NSAIDs are discussed, as are new insights into the role of COX-1/2 for a normal nephrogenesis. COX-nil or COX-inhibited animals have long lasting renal structural injury. Fetuses exposed in utero to significant amounts of NSAIDs have at birth various degrees of renal insufficiency and structural renal defects with a very high mortality.

CONCLUSIONS:

All NSAIDs, both specific and nonspecific COX inhibitors, have renal side effects in the immediate post-natal period and should, therefore, be given with the utmost caution. NSAIDs given during pregnancy for the prevention of toxemia, polyhydramnios and premature labour may affect fetal renal function and structure. In animal experiments, IBU was not less nephrotoxic than INDO, as suggested recently by human premature neonates.     

A comparison of analgesic efficacy of tramadol and pethidine for management of postoperative pain in children: a randomized,controlled study

Prevention of postoperative pain in children is one of the most important objectives of the anesthesiologist. Opioids have been used as an analgesic for postoperative pain in children for many years. Tramadol has both opioid and monoaminergic agonist actions. The aim of the study was to determine if the analgesic potency and occurrence of adverse effects of tramadol differ from pethidine when administered to children. A total of 110 healthy children, aged 2-12 years, scheduled for elective lower abdominal surgery were randomized to receive either pethidine 1 mg/kg (Group I, n = 60) or tramadol 2 mg/kg (Group II, n = 50) for postoperative pain after anesthesia induction. Pain intensity, adverse effects, heart rate, and systolic and diastolic blood pressure were recorded at regular intervals. The mean pain scores on postoperative 24 h were significantly greater with tramadol than with pethidine. Sedation scores, heart rate and systolic and diastolic blood pressure showed no significant differences between the groups. We conclude that pethidine and tramadol are effective in providing analgesia in pediatric patients, but pethidine provided better postoperative analgesia than tramadol. Changes in blood pressure, heart rate and arterial oxygen saturation were minimal and were similar in both drugs.     

The pharmacological treatment of neonatal pain

Optimal analgesia remains a major challenge for all involved in the care of (critically) ill newborns. The rapid changes in liver metabolism involving maturation of liver enzymes and renal clearance of drugs render (extreme) very low birth weight infants different from newborns of later postconceptional age with regards to the use of opioids such as morphine and fentanyl. Acute and/or procedural pain has been investigated fairly recently in randomized controlled trials and there are now guidelines. The long-term effects of opioid use in this particular age group of vulnerable babies await further evaluation.     

Recurrent abdominal pain in children--a retrospective study of outcome in a group referred to a pediatric gastroenterology practice

Recurrent abdominal pain (RAP) affects a significant number of children each year. We reviewed our experience over a 2-year period to determine the outcome of patients who were referred for pediatric gastroenterology consultation. We identified 356 patients, 149 (42%) male and 207 (58%) female. All patients underwent a thorough interview and complete physical examination. Patients suspected of having irritable bowel syndrome (IBS) were treated as such without further initial evaluation. Others underwent an initial blood and urine evaluation. When these initial screening studies were negative, additional studies were performed including abdominal ultrasonography, radiography, and/or endoscopy of the upper gastrointestinal (GI) tract if the history suggested a possible diagnosis that could be excluded or confirmed by such tests. There was no identifiable diagnosis in 43.5% of the patients studied. IBS was diagnosed in 25.8% of all patients. Constipation was diagnosed in 3.7%. Miscellaneous causes, including GI mucosal lesions, and renal and pancreatic disorders were found in an additional 27% of patients. In a follow-up survey, more than 70% of the treated respondents were improved (i.e., their RAP had resolved or was markedly improved). We conclude that most children with RAP have a functional disorder. Patients with an organic cause for pain can be identified and treated in a cost-effective manner with carefully planned evaluation.     

Pain control: opioid dosing, population kinetics and side-effects

Neonates undergoing invasive procedures, postoperative pain or ventilatory support commonly receive opioids for treating pain and stress. Randomized clinical trials have examined the benefits and adverse effects of morphine or fentanyl for ventilated neonates and other indications. This paper summarizes the current evidence for opioid dosing in newborns, reviews their side-effects and explains the use of population kinetics and non-linear mixed-effects modeling to analyze the data from clinical trials. Opioid use should be reserved for severe pain postoperatively or during intensive care in neonates, using continuous infusions rather than intermittent boluses. The safety and efficacy data from prolonged opioid use, particularly on the long-term outcomes of neonates, is still lacking. The pharmacodynamics and pharmacogenetics of opioid use in infancy needs further investigation, using non-linear mixed-effects models to drive individualized therapy. The current interest in opioid research will reap rich dividends in providing pain relief for neonates and avoiding dangerous side effects.     

Effect of grapefruit juice on cyclosporin A pharmacokinetics in pediatric renal transplant patients

Cyclosporin A (CsA) is an important immunosuppressant that is prone to numerous drug interactions. Grapefruit juice has been investigated, as a possible adjunct to CsA dosing in adult renal transplant recipients, to decrease CsA metabolism and reduce dosages. This study investigated this combination in pediatric renal transplant patients. Six stable pediatric renal transplant patients were entered into an open-label, four-period cross-over study in which patients were given their current CsA dose as either an oral solution (CsA-Sol) or a microemulsion (CsA-ME). In addition, drugs were administered concurrently with water or grapefruit juice. Steady-state pharmacokinetic profiles were taken during each of the four periods. Following the concurrent administration of grapefruit juice, CsA whole-blood 12-h trough levels were significantly increased during CsA-Sol dosing. Furthermore, the CsA elimination rate constant was significantly reduced during the same period. After CsA-ME dosing, no differences in CsA pharmacokinetics were found between concurrent water or grapefruit ingestion. Grapefruit juice co-administration reduced the production of CsA metabolites, AM1 and AM9, during CsA-Sol dosing. No changes in CsA metabolite production were found when patients were given CsA-ME with grapefruit juice as compared with water. Hence, alterations in CsA absorption and elimination occur with concurrent grapefruit juice ingestion when stable pediatric renal transplant patients are taking the oral CsA solution, but not the microemulsion formulation. These changes may be mediated by alterations in intestinal or hepatic metabolism, or drug absorption. The effect of grapefruit juice on CsA absorption is not readily predictable in these patients.     

Safety and efficacy of remifentanil in craniosynostosis repair in children less than 1 year old

Few studies on analgesia with remifentanil (Rf) in children are available, and there are no data on the use of this drug in pediatric neurosurgery. Rf is a new mu-receptor opioid agonist, acting through the activation of pain inhibitory mechanisms. We conducted a prospective trial on the analgesic effects of Rf in 20 children less than 1 year of age undergoing a neurosurgical procedure for craniosynostosis repair. Rf was administered at doses of 0.25 microgram/kg/min, by continuous infusion, 1 h after admission to the pediatric intensive care unit (PICU). The treatment was prolonged for 12 h after the operation. The postoperative pain was evaluated in our PICU, comparing the changing of behavioral (AFS and CHEOPS score) and hemodynamic (heart rate, respiratory rate, systolic and diastolic blood pressure, oxygen saturation, O(2) and CO(2) partial pressure) parameters, before and after treatment with Rf. This drug showed a satisfactory pain control in all the children treated. No significant side effects were noticed, except for one episode of urinary retention. In conclusion, Rf appears to be safe and effective for the treatment of acute pain in the very young child submitted to craniosynostosis repair.     

急诊科小儿镇痛和镇静的研究进展

小儿急诊治疗时常伴有外伤或疼痛.在急诊诊治期间,可能有必要进行某些疼痛或令人不适的诊疗操作.临床上需要急诊科医生为小儿提供安全、有效的镇痛和镇静.为此,我们对国外已发表的相关研究结果做一综述,主要包括以下几个方面:确保在急诊时小儿不会经受长时间或额外的疼痛;使用综合评估工具评估疼痛以分诊患儿;选择适当的药物、剂量和途径,在首次疼痛处理时即提供有效镇痛;尽可能选择无痛苦的方式给药(经鼻、调味糖浆)等;经常再次评估疼痛分数以确保有效镇痛,并留有足够时间来等待药物起效,同时使用非药理和药理的模式镇痛;避免"常规"进行一些不必要的致痛的侵入性操作;使用表面麻醉、局部麻醉和区域麻醉连同适当的安全程序镇静,以避免疼痛加剧.