|
1
|
Swain A, Nag DS, Sahu S, Samaddar DP. Adjuvants to local anesthetics: Current understanding and future trends. World J Clin Cases 2017; 5:307-323. [PMID: 28868303 PMCID: PMC5561500 DOI: 10.12998/wjcc.v5.i8.307] [Citation(s) in RCA: 120] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2017] [Revised: 05/03/2017] [Accepted: 05/19/2017] [Indexed: 02/05/2023] Open
Abstract
Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by its duration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action. A large array of opioids ranging from morphine, fentanyl and sufentanyl to hydromorphone, buprenorphine and tramadol has been used with varying success. However, their use has been limited by their adverse effect like respiratory depression, nausea, vomiting and pruritus, especially with its neuraxial use. Epinephrine potentiates the local anesthetics by its antinociceptive properties mediated by alpha-2 adrenoreceptor activation along with its vasoconstrictive properties limiting the systemic absorption of local anesthetics. Alpha 2 adrenoreceptor antagonists like clonidine and dexmedetomidine are one of the most widely used class of local anesthetic adjuvants. Other drugs like steroids (dexamethasone), anti-inflammatory agents (parecoxib and lornoxicam), midazolam, ketamine, magnesium sulfate and neostigmine have also been used with mixed success. The concern regarding the safety profile of these adjuvants is due to its potential neurotoxicity and neurological complications which necessitate further research in this direction. Current research is directed towards a search for agents and techniques which would prolong local anaesthetic action without its deleterious effects. This includes novel approaches like use of charged molecules to produce local anaesthetic action (tonicaine and n butyl tetracaine), new age delivery mechanisms for prolonged bioavailability (liposomal, microspheres and cyclodextrin systems) and further studies with other drugs (adenosine, neuromuscular blockers, dextrans).
Collapse
|
|
2
|
Esophageal Atresia/Tracheoesophageal Fistula Repair Complicated by Tracheomalacia: A Case Report of Successful Management of Respiratory Distress Using Caudal Morphine. ACTA ACUST UNITED AC 2017; 9:28-30. [PMID: 28410264 DOI: 10.1213/xaa.0000000000000517] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
We report a case of severe respiratory distress in a neonate who was not endotracheally intubated soon after esophageal atresia/tracheoesophageal fistula (EA/TEF) repair. In this serious situation, any form of emergency respiratory support or definitive airway management may compromise the esophageal anastomosis and fistula repair. The cause of respiratory distress in the early postoperative period after EA/TEF is multifactorial, and in this case, included symptomatic tracheomalacia, which is commonly associated with EA/TEF.
Collapse
|
|
3
|
Anand KJS, Willson DF, Berger J, Harrison R, Meert KL, Zimmerman J, Carcillo J, Newth CJL, Prodhan P, Dean JM, Nicholson C, Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Tolerance and withdrawal from prolonged opioid use in critically ill children. Pediatrics 2010; 125:e1208-25. [PMID: 20403936 PMCID: PMC3275643 DOI: 10.1542/peds.2009-0489] [Citation(s) in RCA: 218] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
OBJECTIVE After prolonged opioid exposure, children develop opioid-induced hyperalgesia, tolerance, and withdrawal. Strategies for prevention and management should be based on the mechanisms of opioid tolerance and withdrawal. PATIENTS AND METHODS Relevant manuscripts published in the English language were searched in Medline by using search terms "opioid," "opiate," "sedation," "analgesia," "child," "infant-newborn," "tolerance," "dependency," "withdrawal," "analgesic," "receptor," and "individual opioid drugs." Clinical and preclinical studies were reviewed for data synthesis. RESULTS Mechanisms of opioid-induced hyperalgesia and tolerance suggest important drug- and patient-related risk factors that lead to tolerance and withdrawal. Opioid tolerance occurs earlier in the younger age groups, develops commonly during critical illness, and results more frequently from prolonged intravenous infusions of short-acting opioids. Treatment options include slowly tapering opioid doses, switching to longer-acting opioids, or specifically treating the symptoms of opioid withdrawal. Novel therapies may also include blocking the mechanisms of opioid tolerance, which would enhance the safety and effectiveness of opioid analgesia. CONCLUSIONS Opioid tolerance and withdrawal occur frequently in critically ill children. Novel insights into opioid receptor physiology and cellular biochemical changes will inform scientific approaches for the use of opioid analgesia and the prevention of opioid tolerance and withdrawal.
Collapse
Affiliation(s)
- Kanwaljeet J S Anand
- Department of Pediatrics, Le Bonheur Children's Hospital and University of Tennessee Health Science Center, Memphis, Tennessee, USA.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
4
|
Pypendop BH, Siao KT, Pascoe PJ, Ilkiw JE. Effects of epidurally administered morphine or buprenorphine on the thermal threshold in cats. Am J Vet Res 2008; 69:983-7. [PMID: 18672960 DOI: 10.2460/ajvr.69.8.983] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To determine the antinociceptive effects of epidural administration of morphine or buprenorphine in cats by use of a thermal threshold model. ANIMALS 6 healthy adult cats. PROCEDURES Baseline thermal threshold was determined in duplicate. Cats were anesthetized with isoflurane in oxygen. Morphine (100 microg/kg diluted with saline [0.9% NaCl] solution to a total volume of 0.3 mL/kg), buprenorphine (12.5 microg/kg diluted with saline solution to a total volume of 0.3 mL/kg), or saline solution (0.3 mL/kg) was administered into the epidural space according to a Latin square design. Thermal threshold was determined at various times up to 24 hours after epidural injection. RESULTS Epidural administration of saline solution did not affect thermal threshold. Thermal threshold was significantly higher after epidural administration of morphine and buprenorphine, compared with the effect of saline solution, from 1 to 16 hours and 1 to 10 hours, respectively. Maximum (cutout) temperature was reached without the cat reacting in 0, 74, and 11 occasions in the saline solution, morphine, and buprenorphine groups, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Epidural administration of morphine and buprenorphine induced thermal antinociception in cats. At the doses used in this study, the effect of morphine lasted longer and was more intense than that of buprenorphine.
Collapse
Affiliation(s)
- Bruno H Pypendop
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
| | | | | | | |
Collapse
|
|
5
|
Abstract
BACKGROUND Postoperative pain management in children is often empirical rather than evidence based. Morphine is the pharmacological treatment most widely used and although considered safe for children, adequate scientific data on morphine's pharmacokinetics, efficacy and safety are lacking. This systematic review aimed to evaluate the available literature examining different pediatric morphine regimens with respect to dosage, analgesic efficacy and incidence of side effects. METHODS Thirty-six randomized, double-blind controlled clinical trials with 49 comparisons, including multiple dosage regimens and routes of administration were included. The primary outcome measures for analgesic efficacy (pain intensity, time to first analgesic request and need for rescue analgesics) together with the incidence of morphine-related side effects were evaluated qualitatively by significant difference (P < 0.05) as reported in the original investigations. RESULTS Overall, significant improvements in the defined outcome measures on analgesic efficacy were only observed when morphine was compared with inactive control interventions. No relation between morphine dosage and analgesic efficacy was detected. The most common morphine-related side effects were vomiting and sedation, with significantly higher incidences observed after morphine administration in half of all comparisons. CONCLUSIONS Although several factors may justify its use as first line therapy in many parts of the world, morphine alone is not the most suitable analgesic for postoperative pain in pediatric patients, as it does not have superior analgesic effect and a higher incidence of side effects compared with active control interventions. More standardized clinical trials with multimodal regimens as well as guidelines for evaluating pediatric medicines are desirable in the future.
Collapse
Affiliation(s)
- Tina Hoff Duedahl
- Department of Pharmacology and Pharmacotherapy, University of Copenhagen, Copenhagen, Denmark.
| | | |
Collapse
|
|
6
|
Anand KJS, Johnston CC, Oberlander TF, Taddio A, Lehr VT, Walco GA. Analgesia and local anesthesia during invasive procedures in the neonate. Clin Ther 2006; 27:844-76. [PMID: 16117989 DOI: 10.1016/j.clinthera.2005.06.018] [Citation(s) in RCA: 81] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/20/2005] [Indexed: 11/30/2022]
Abstract
BACKGROUND Preterm and full-term neonates admitted to the neonatal intensive care unit or elsewhere in the hospital are routinely subjected to invasive procedures that can cause acute pain. Despite published data on the complex behavioral, physiologic, and biochemical responses of these neonates and the detrimental short- and long-term clinical outcomes of exposure to repetitive pain, clinical use of pain-control measures in neonates undergoing invasive procedures remains sporadic and suboptimal. As part of the Newborn Drug Development Initiative, the US Food and Drug Administration and the National Institute of Child Health and Human Development invited a group of international experts to form the Neonatal Pain Control Group to review the therapeutic options for pain management associated with the most commonly performed invasive procedures in neonates and to identify research priorities in this area. OBJECTIVE The goal of this article was to review and synthesize the published clinical evidence for the management of pain caused by invasive procedures in preterm and full-term neonates. METHODS Clinical studies examining various therapies for procedural pain in neonates were identified by searches of MEDLINE (1980-2004), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 1, 2004), the reference lists of review articles, and personal files. The search terms included specific drug names, infant-newborn, infant-preterm, and pain, using the explode function for each key word. The English-language literature was reviewed, and case reports and small case series were discarded. RESULTS The most commonly performed invasive procedures in neonates included heel lancing, venipuncture, IV or arterial cannulation, chest tube placement, tracheal intubation or suctioning, lumbar puncture, circumcision, and SC or IM injection. Various drug classes were examined critically, including opioid analgesics, sedative/hypnotic drugs, nonsteroidal anti-inflammatory drugs and acetaminophen, injectable and topical local anesthetics, and sucrose. Research considerations related to each drug category were identified, potential obstacles to the systematic study of these drugs were discussed, and current gaps in knowledge were enumerated to define future research needs. Discussions relating to the optimal design for and ethical constraints on the study of neonatal pain will be published separately. Well-designed clinical trials investigating currently available and new therapies for acute pain in neonates will provide the scientific framework for effective pain management in neonates undergoing invasive procedures.
Collapse
Affiliation(s)
- K J S Anand
- Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, USA.
| | | | | | | | | | | |
Collapse
|
|
7
|
Lejus C, Surbled M, Schwoerer D, Renaudin M, Guillaud C, Berard L, Pinaud M. Postoperative epidural analgesia with bupivacaine and fentanyl: hourly pain assessment in 348 paediatric cases. Paediatr Anaesth 2001; 11:327-32. [PMID: 11359592 DOI: 10.1046/j.1460-9592.2001.00659.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND The objective of this prospective study was the evaluation of the analgesia provided by an epidural infusion of bupivacaine and fentanyl after different types of surgery in children. METHODS Data were collected from 348 epidural analgesia in 87 children below 2 years of age, in 80 children between 2 and 6 years and 181 above 6 years of age, for a median duration of 43 postoperative hours. Bupivacaine (mean concentration 0.185%) and fentanyl (5 microg.kg-1.day-1) were administered on the surgical ward. RESULTS Pain control was considered excellent in 86% of the 11 072 pain hourly assessments. Analgesia was found to be better for children older than 2 years, and the overall quality of their night's sleep was better than that of older children. Higher pain scores were noted for Nissen fundoplication surgery and club foot repairs. Early discontinuation rarely occurred, and only because of technical problems with the epidural catheter (4%) or insufficient analgesia (6%). Complications were minor (nausea/vomiting 14%, pruritus 0.6%, urinary retention 17%) and easily reversed. CONCLUSIONS This combination of bupivacaine-fentanyl provides safe analgesia after major surgery in children with frequent clinical monitoring. Regular pain assessments of intensity and duration are useful to improve the quality of postoperative analgesia.
Collapse
MESH Headings
- Adolescent
- Analgesia, Epidural/adverse effects
- Analgesics, Opioid/administration & dosage
- Analgesics, Opioid/adverse effects
- Analgesics, Opioid/therapeutic use
- Anesthetics, Local/administration & dosage
- Anesthetics, Local/adverse effects
- Anesthetics, Local/therapeutic use
- Bupivacaine/administration & dosage
- Bupivacaine/adverse effects
- Bupivacaine/therapeutic use
- Child
- Child, Preschool
- Female
- Fentanyl/administration & dosage
- Fentanyl/adverse effects
- Fentanyl/therapeutic use
- Humans
- Infant
- Infant, Newborn
- Male
- Pain Measurement/drug effects
- Pain, Postoperative/drug therapy
- Prospective Studies
- Sleep/drug effects
Collapse
Affiliation(s)
- C Lejus
- Service d'Anaesthésie et de Réanimation Chirurgicale, Hôtel Dieu, 44093 Nantes, Cedex 01, France.
| | | | | | | | | | | | | |
Collapse
|
|
8
|
|
|
9
|
Abstract
Laboratory data, economic pressures, and the wish for humane treatment have been some of the driving forces behind improvements in paediatric pain management. Within the space of 10 years, there have been dramatic changes in the quality of treatment received by children undergoing surgical operations. Moreover, those receiving medical treatment, for example, sickle cell disease, have also benefited from increased experience in pain management. Children receiving care in specialised centres can now expect to benefit from up-to-date techniques of pain management, such as patient-controlled analgesia, nurse-controlled analgesia, and epidural infusions. They will be managed by ward nurses experienced and trained in paediatric pain relief, they will be attended by nurses whose special interest and training is the management of children's pain, and they will be provided with the techniques of analgesia by competent, trained anaesthetic staff. Improved care, with close attention to pain relief, is not only humane, but improves the patient turnaround by enhancing rapid discharge. Further education is required to spread these benefits to children being managed outside highly specialised centres. Not only education, but investment, is needed also to ensure that all children receive a standard of care second to none.
Collapse
Affiliation(s)
- A R Lloyd-Thomas
- Department of Anaesthesia, Great Ormond Street Hospital for Children NHS Trust, London, UK.
| |
Collapse
|
|
10
|
Chabas E, Gomar C, Villalonga A, Sala X, Taura P. Postoperative respiratory function in children after abdominal surgery. A comparison of epidural and intramuscular morphine analgesia. Anaesthesia 1998; 53:393-7. [PMID: 9613308 DOI: 10.1046/j.1365-2044.1998.00325.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Thirty children undergoing urological and abdominal surgery were entered into a randomised trial comparing the effects of epidural and intramuscular morphine on postoperative respiratory function. The forced vital capacity and the forced expired volume in 1 s were measured before and 6 h after surgery and on each of the following seven days. Significant decreases (p < 0.01) in forced vital capacity and forced expired volume in 1 s were seen after surgery. After the first postoperative day, a gradual recovery in pulmonary function was observed but the measured parameters had not returned to their pre-operative control values by the end of the study. There were no statistically significant differences between the two groups during the study with respect to forced vital capacity and forced expired volume in 1 s. The quality of analgesia was better in the epidural morphine group than in the intramuscular morphine group. The incomplete recovery of pulmonary function suggests that pain is not the only cause of postoperative respiratory changes in these patients.
Collapse
Affiliation(s)
- E Chabas
- Department of Anaesthesia, Hospital Clinic, Barcelona, Spain
| | | | | | | | | |
Collapse
|
|
11
|
Kart T, Walther-Larsen S, Svejborg TF, Feilberg V, Eriksen K, Rasmussen M. Comparison of continuous epidural infusion of fentanyl and bupivacaine with intermittent epidural administration of morphine for postoperative pain management in children. Acta Anaesthesiol Scand 1997; 41:461-5. [PMID: 9150772 DOI: 10.1111/j.1399-6576.1997.tb04724.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND The aim of this study was to compare epidural infusion of bupivacaine and fentanyl and intermittent epidural morphine with regard to analgesic effect, and incidence and severity of side effects in children undergoing major abdominal or genito-urological surgery in order to improve the postoperative pain management of children. METHODS A double-blind, block-randomised study design was used. Thirty-one children aged 3 months to 6 years undergoing major abdominal or genito-urological surgery were studied. After induction of anaesthesia a lumbar epidural catheter was placed at L3-4 or L4-5. Postoperatively, the children received either 30 micrograms/kg of morphine every 8 h or a continuous infusion of fentanyl 2 micrograms/ml and bupivacaine 1.0 mg/ml at a rate of 0.25 ml.kg-1.h-1. All children additionally received rectal paracetamol in doses of 50-100 mg.kg-1.d-1 on a regular basis, and amol in doses of 50-100 mg.kg-1.d-1 on a regular basis, and if necessary supplementary intravenous morphine in doses of 50 micrograms/kg. Postoperatively, pain, administration of supplemental morphine and side effects were recorded 5 times by one observer during the day of surgery and the first postoperative day. All children had an epidural catheter throughout the study period. RESULTS Both regimens provided effective analgesia, but significantly better pain relief was obtained in children receiving the fentanyl/bupivacaine regimen. Sedation, pruritus, vomiting, and administration of antiemetics were seen in both treatment groups, and even though both the incidence and severity of side effects tended to be higher in children receiving morphine, no statistically significant difference was found. No episodes of respiratory depression or motor blockade were noticed. CONCLUSIONS Continuous epidural infusion of fentanyl and bupivacaine was found to be superior to intermittent epidural morphine. The initial regimen should be fentanyl 2 micrograms/ml and bupivacaine 1.0 mg/ml infused at a rate of 0.25 ml.kg-1.h-1.
Collapse
Affiliation(s)
- T Kart
- Department of Anaesthesia, Rigshospitalet, Copenhagen, Denmark
| | | | | | | | | | | |
Collapse
|
|
12
|
Kart T, Christrup LL, Rasmussen M. Recommended use of morphine in neonates, infants and children based on a literature review: Part 2--Clinical use. Paediatr Anaesth 1997; 7:93-101. [PMID: 9188108 DOI: 10.1111/j.1460-9592.1997.tb00488.x] [Citation(s) in RCA: 78] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
The indication for morphine use is primarily pain, but also a combined analgesic and sedative effect may be the rationale behind morphine administration. Paediatric morphine regimens have been reported for children with postoperative pain, pain related to cancer, sickle cell crisis pain, burns and AIDS. No dose response curve for morphine in neonates, infants or children has been established, and different levels for the minimum effective plasma concentration have been estimated. The side effects observed in neonates, infants, and children are similar to those observed in adults, and neonates do not seem to be more susceptible to respiratory depression than older children. Despite shortcomings in the knowledge of the pharmacodynamics of morphine, it can be considered safe to administer morphine to neonates, infants or children. Initial regimens has been calculated from the pharmacokinetic parameters of morphine, but treatment must be adjusted according to analgesic effect and incidence of side effects.
Collapse
Affiliation(s)
- T Kart
- Royal Danish School of Pharmacy, Department of Pharmaceutics, Copenhagen, Denmark
| | | | | |
Collapse
|
|
13
|
Rainov NG, Gutjahr T, Burkert W. Intra-operative epidural morphine, fentanyl, and droperidol for control of pain after spinal surgery. A prospective, randomized, placebo-controlled, and double-blind trial. Acta Neurochir (Wien) 1996; 138:33-9. [PMID: 8686522 DOI: 10.1007/bf01411721] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
The present study was conducted to investigate the analgesic effects of intra-operatively administered epidural morphine in patients undergoing surgery for lumbar disc disease. Three treatment groups were constituted: one with 5.0 mg morphine and 2.5 mg dehydrobenzperidol (DHB) in 10 ml physiological saline, one with 5.0 mg morphine and 0.1 mg fentanyl in the same amount of saline, and one placebo group with saline only. The test solution was injected epidurally via catheter after haemostasis and before closure of the wound. Sixty eight patients were randomly assigned to each of the three groups and subjected to a double-blind evaluation. In the morphine/fentanyl and morphine/droperidol groups, significantly better analgesia was found as compared to the placebo group. No significant difference was found between the morphine/fentanyl and morphine/droperidol groups considering side effects of therapy, as well as duration and quality of analgesia. The side effects in the treatment groups were only slight and not significantly different from the placebo group. It was shown that additional epidural fentanyl offers no significant improvement of postoperative analgesia. No significant reduction of adverse effects could be found in the morphine/droperidol group compared to the morphine/fentanyl group. In conclusion, the intra-operative epidural application of morphine is a safe, effective and simple method for achieving sufficient analgesia in the first 24 hours after lumbar spinal surgery for disc disease.
Collapse
Affiliation(s)
- N G Rainov
- Neurosurgical Department, Faculty of Medicine, Martin-Luther-University Halle-Wittenberg, Federal Republic of Germany
| | | | | |
Collapse
|
|
14
|
|